7-Hydroxylation of warfarin is strongly inhibited by sesamin, but not by episesamin, caffeic and ferulic acids in human hepatic microsomes Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-17 Nadezhda Pilipenko, Martin Krøyer Rasmussen, Olena Doran, Galia Zamaratskaia
Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamincontaining food or dietary supplements in warfarin-treated patients need to be further studied.
Lanthanum chloride impairs memory in rats by disturbing the glutamate-glutamine cycle and over-activating NMDA receptors Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-17 Xiaoyu Hu, Jinghua Yang, Yaling Sun, Xiang Gao, Lijin Zhang, Yingqi Li, Miao Yu, Shiyu Liu, Xiaobo Lu, Cuihong Jin, Shengwen Wu, Yuan Cai
Studies have reported that lanthanum chloride (LaCl3) can across the blood-brain barrier, accumulate in the brain and affect the spatial learning and memory abilities. However, the potential mechanism that LaCl3-induced neurotoxic effects has not yet been defined. Glutamate (Glu) is a vital excitatory neurotransmitter, and the excessive Glu accumulation in extracellular space can induce excitatory neurotoxicity. This study was designed to research the influence of LaCl3 on the spatial learning and memory abilities of rats and to discuss the possible mechanism underlying this effect regarding the extracellular Glu concentration, the Glu-glutamine (Gln) cycle and the N-methyl-D-aspartate (NMDA) receptors. Four groups of Wistar rats were exposed to 0%, 0.125%, 0.25% or 0.5% LaCl3 via the drinking water from the day of conception to 1 month after weaning. These results showed that LaCl3 exposure damaged spatial learning and memory, long-term potentiation, and neuronal ultrastructure, generated an excessive accumulation of glutamate, significantly decreased the expression of glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), glutamine synthetase (GS) and phosphate-activated glutaminase (PAG), and increased the expression of GluN1, GluN2A and GluN2B. This study showed that LaCl3 impaired the rats' spatial learning and memory abilities by disturbing the Glu-Gln cycle and over-activating NMDA receptors thereby inducing excitotoxicity.
Effects of warfarin on biological processes other than haemostasis: A review Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-17 Aleksandra Popov Aleksandrov, Ivana Mirkov, Marina Ninkov, Dina Mileusnic, Jelena Demenesku, Vesna Subota, Dragan Kataranovski, Milena Kataranovski
Warfarin is the world's most widely used anticoagulant drug. Its anticoagulant activity is based on the inhibition of the vitamin K-dependent (VKD) step in the complete synthesis of a number of blood coagulation factors that are required for normal blood coagulation. Warfarin also affects synthesis of VKD proteins not related to haemostasis including those involved in bone growth and vascular calcification. Antithrombotic activity of warfarin is considered responsible for some aspects of its anti-tumour activity of warfarin. Some aspects of activities against tumours seem not to be related to haemostasis and included effects of warfarin on non-haemostatic VKD proteins as well as those not related to VKD proteins. Inflammatory/immunomodulatory effects of warfarin indicate much broader potential of action of this drug both in physiological and pathological processes. This review provides an overview of the published data dealing with the effects of warfarin on biological processes other than haemostasis.
Concentrations of arsenic and lead in rice (Oryza sativa L.) in Iran: A systematic review and carcinogenic risk assessment Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-16 Yadolah Fakhri, Geir Bjørklund, Anoushiravan Mohseni Bandpei, Salvatore Chirumbolo, Hassan Keramati, Rokhsane Hosseini Pouya, Anvar Asadi, Nazak Amanidaz, Mansour Sarafraz, Amir Sheikhmohammadi, Zahra Baninameh, Seyed Mohsen Mohseni, Maryam Sarkhosh, Seyed Mehdi Ghasemi
Cholesterol modulates the liposome membrane fluidity and permeability for a hydrophilic molecule Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-12 Samar Kaddah, Nathalie Khreich, Fouad Kaddah, Catherine Charcosset, Hélène Greige-Gerges
The effect of cholesterol (CHOL) content on the permeability and fluidity of dipalmitoylphosphatidylcholine (DPPC) liposome membrane was investigated. Liposomes encapsulating sulforhodamine B (SRB), a fluorescent dye, were prepared by reverse phase evaporation technique (REV) at various DPPC:CHOL molar ratios (from 100:0 to 100:100). The release kinetics of SRB was studied during 48 h in buffer (pH 7.4) containing NaCl at 37 °C. The DPPC:CHOL formulations were also characterized for their size, polydispersity index and morphology. Increasing CHOL concentration induced an increase in the mean liposomes size accompanying with a shape transition from irregular to nanosized, regular and spherical vesicles. The release kinetics of SRB showed a biphasic pattern; the release data was then analyzed using different mathematical models. On the overall, the SRB release was governed by a non-Fickian diffusion during the first period (0–10 h) while it followed a Fickian diffusion between 10 and 48 h. Changes in DPPC liposome membrane fluidity of various batches (CHOL% 0, 10, 20, 30 and 100) were monitored by using 5- and 16 doxyl stearic acids (DSA) as spin labels. CHOL induced a decrease in the bilayer fluidity. Concisely, CHOL represents a critical component in modulating the release of hydrophilic molecules from lipid vesicles.
Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-11 Tiane C. Finimundy, Rui M.V. Abreu, Natalia Bonetto, Fernando J. Scariot, Aldo J.P. Dillon, Sergio Echeverrigaray, Lillian Barros, Isabel C.F.R. Ferreira, João A.P. Henriques, Mariana Roesch-Ely
Protective effect of flavonoids from Cyclocarya paliurus leaves against carbon tetrachloride-induced acute liver injury in mice Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-11 Jianhua Xie, Wenjie Wang, Caijun Dong, Lixin Huang, Hui Wang, Chang Li, Shaoping Nie, Mingyong Xie
Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus), known locally as ‘sweet tea tree’, is commonly cultivated in China. Flavonoids from Cyclocarya paliurus (Batal.) Iljinskaja (FC) is reported to exhibit multiple biological effects, including anti-inflammatory, anti-oxidant and anti-diabetic activities. However, their influence on carbon tetrachloride (CCl4)-induced acute liver injury remains unclear. This study was designed to investigate the hepatoprotective effect of total flavonoids from C. paliurus leaves. Results revealed that flavonoids from C. paliurus significantly decreased CCl4-induced elevation of activities of aspartate transaminase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) as well as the level of malondialdehyde (MDA), and markedly increased the levels of SOD, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) compared with the model group. Structures of mainly compounds were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) spectroscopic and chemical analyses. This study clearly shows that flavonoids from C. paliurus exert a potent protective effect against CCl4-induced acute liver injury in mice. Its hepatoprotective effect appears to be closely associated with its antioxidant activity. The results indicated that flavonoids from C. paliurus leaves could be considered as a potent food supplement in the prevention of acute liver injury.
Monitoring the prevalence of genetically modified (GM) maize in Iran food products Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-11 Motahreh Sadat Hosseini, Gilda Eslami, Bahador Hajimohammadi, Hossein Fallahzadeh, Zahra derakhshan, Gea Oliveri Conti, Margherita Ferrante
Maize, the second most important genetically modified (GM) crop, and an ingredient in many foodstuffs worldwide. Regulations for both the labeling and the traceability of GMOs in feed chains are coming into force worldwide. To provide consumer's information, labelling for food products containing more than 0.9% of GM material is demanded by the actual EU legislation. Analysis of foods is then essential to detect and quantify GM maize material and verify the compliance with labelling information. For this purpose, reliable and accurate detection methods are a necessity. PCR-based methods are the most common and reliable methods developed thus far. The aim of the present work was to assess the presence of GM maize in a range of processed foods commercialised in Iran from 2016–2017. For this purpose, screening of GM material was carried out by qualitative PCR. According to results, 26% of the samples tested were positive for GMOs. The present study which represents a fast and reliable methodology would provide an overview of the presence and levels of GMOs maize in Iran. While, results demonstrate for the first time the screening for GMOs in foods sold in Iran with a large time scale and wide product scope.
Aronia melanocarpa fruit juice ameliorates the symptoms of inflammatory bowel disease in TNBS-induced colitis in rats Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-11 Stefka Valcheva-Kuzmanova, Atanas Kuzmanov, Vasilena Kuzmanova, Maria Tzaneva
Trinitrobenzensulfonic acid (TNBS) is commonly used to induce an experimental inflammatory bowel disease (IBD) model. Oxidative stress and inflammation have been proposed as mechanisms underlying the pathophysiology of IBD. Aronia melanocarpa fruit juice (AMFJ) is extremely rich in polyphenolic substances, mainly proanthocyanidins, flavonoids and phenolic acids. The aim of this study was to evaluate the effect of AMFJ in a rat TNBSinduced colitis model and to compare the effect of the juice with that of sulfasalazine. Colitis was induced by TNBS in male Wistar rats. After the induction of colitis, AMFJ at three doses (2.5, 5 and 10 ml/kg) and sulfasalazine (400 mg/kg) were administered orally till the 14th experimental day. Severity of colitis was assessed by macroscopic and histopathological criteria. Oxidative stress was evaluated by the concentration of thiobarbituric acid reactive substances (TBARS). TNBS caused severe colonic damage. AMFJ dose-dependently ameliorated TNBS-induced colitis. It improved the macroscopic and microscopic signs of colitis, and prevented the increase of colonic TBARS concentrations. Regarding different indices, the effect of AMFJ was comparable or even higher than that of sulfasalazine. In conclusion, the ameliorative effects of AMFJ in the experimental TNBSinduced colitis might be the result of its potent antioxidant and antiinflammatory properties.
Internal exposure-based pharmacokinetic evaluation of potential for biopersistence of 6:2 fluorotelomer alcohol (FTOH) and its metabolites Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-11 Shruti V. Kabadi, Jeffrey Fisher, Jason Aungst, Penelope Rice
Polyfluorinated compounds (PFCs) are authorized for use as greaseproofing agents in food contact paper. As C8-PFCs (8-carbons) are known to accumulate in tissues, shorter-chain C6-PFCs (6-carbons) have replaced C8-PFCs in many food contact applications. However, the potential of C6-PFCs for human biopersistence has not been fully evaluated. For the first time, we provide internal exposure estimates to key metabolites of 6:2 fluorotelomer alcohol (6:2 FTOH), a monomeric component of C6-PFCs, to extend our understanding of exposure beyond estimates of external exposure. Pharmacokinetic data from published rat and human studies on 6:2 FTOH were used to estimate clearance and area under the curve (AUC) for its metabolites: 5:3 fluorotelomer carboxylic acid (5:3 A), perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA). Internal exposure to 5:3 A was the highest of evaluated metabolites across species and it had the slowest clearance. Additionally, 5:3 A clearance decreased with increasing 6:2 FTOH exposure. Our analysis provides insight into association of increased internal 5:3 A exposure with high biopersistence potential of 6:2 FTOH. Our results identify 5:3 A as an important biomarker of internal 6:2 FTOH exposure for use in biomonitoring studies, and are potentially useful for toxicological assessment of chronic dietary 6:2 FTOH exposure.
In vitro assessment of silver nanoparticles immunotoxicity Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-10 Valentina Galbiati, Laura Cornaghi, Elisabetta Gianazza, Marco A. Potenza, Elena Donetti, Marina Marinovich, Emanuela Corsini
This study aimed to characterize unwanted immune effects of nanoparticles (NP) using THP-1 cells, human whole blood and enriched peripheral blood monocytes. Commercially available silver NP (AgNP < 100 nm, also confirmed by Single Particle Extinction and Scattering) were used as prototypical NP. Cells were treated with AgNP alone or in combination with classical immune stimuli (i.e. LPS, PHA, PWM) and cytokine assessed; in addition, CD54 and CD86 expression was evaluated in THP-1 cells. AgNP alone induced dose-related IL-8 production in all models, with higher response observed in THP-1 cells, possibly connected to different protein corona formation in bovine versus human serum. AgNP potentiated LPS-induced IL-8 and TNF-α, but not LPS-induced IL-10. AgNP alone induced slight increase in IL-4, and no change in IFN-γ production. While responses to PHA in term of IL-4 and IFN-γ production were not affected, increased PWM-induced IL-4 and IFN-γ production were observed, suggesting potentiation of humoral response. Reduction in PHA-induced IL-10 was observed. Overall, results indicate immunostimulatory effects. THP-1 cells work as well as primary cells, representing a useful and practical alternative, with the awareness that from a physiological point of view the whole blood assay is the one that comes closest to reality.
Deoxynivalenol, gut microbiota and immunotoxicity: A potential approach? Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-10 Yuxiao Liao, Zhao Peng, Liangkai Chen, Andreas K. Nüssler, Liegang Liu, Wei Yang
Investigation of IN vitro genotoxic effects of an anti-diabetic drug sitagliptin Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-06 Deniz Yuzbasioglu, Cemile Enguzel-Alperen, Fatma Unal
Sitagliptin is an active ingredient of antidiabetic drug used in the treatment of type 2 diabetes mellitus (T2DM). In this study, the genotoxic effects of sitagliptin were determined in human lymphocytes by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. 31.25–1000 μg/mL concentrations of sitagliptin were used. Sitagliptin significantly increased the frequency of CAs and SCEs at the highest concentration at 24 h treatment and all concentrations (except 250 μg/mL for CA, except 31.25 and 62.50 μg/mL for SCE) at 48 h treatment compared with solvent control (DMSO). This compound increased the MN at only the highest concentration compared with the solvent control. Mitotic index (MI) significantly decreased at the three highest concentrations of sitagliptin at 48 h treatment. However, replication (RI) and nuclear division (NDI) indices were not affected at all the treatments. Comet assay results indicated that sitagliptin significantly increased mean comet tail intensity and tail moment at only two concentrations (62.50 and 1000 μg/mL for intensity, 125 and 1000 μg/mL for tail moment), and tail length at all concentrations (except 125 and 500 μg/mL). It was concluded that higher concentration of sitagliptin had genotoxic effects in the human lymphocytes in vitro.
Comprehensive evaluation of the flavonol anti-oxidants, alpha-glycosyl isoquercitrin and isoquercitrin, for genotoxic potential Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-06 Cheryl A. Hobbs, Mihoko Koyanagi, Carol Swartz, Jeffrey Davis, Sawako Kasamoto, Robert Maronpot, Leslie Recio, Shim-mo Hayashi
Quercetin and its glycosides possess potential benefits to human health. Several flavonols are available to consumers as dietary supplements, promoted as anti-oxidants; however, incorporation of natural quercetin glycosides into food and beverage products has been limited by poor miscibility in water. Enzymatic conjugation of multiple glucose moieties to isoquercitrin to produce alpha-glycosyl isoquercitrin (AGIQ) enhances solubility and bioavailability. AGIQ is used in Japan as a food additive and has been granted generally recognized as safe (GRAS) status. However, although substantial genotoxicity data exist for quercetin, there is very little available data for AGIQ and isoquercitrin. To support expanded global marketing of food products containing AGIQ, comprehensive testing of genotoxic potential of AGIQ and isoquercitrin was conducted according to current regulatory test guidelines. Both chemicals tested positive in bacterial reverse mutation assays, and exposure to isoquercitrin resulted in chromosomal aberrations in CHO-WBL cells. All other in vitro mammalian micronucleus and chromosomal aberration assays, micronucleus and comet assays in male and female B6C3F1 mice and Sprague Dawley rats, and Muta™ mouse mutation assays evaluating multiple potential target tissues, were negative for both chemicals. These results supplement existing toxicity data to further support the safe use of AGIQ in food and beverage products.
Ochratoxin A: Toxicity, oxidative stress and metabolism Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-05 Yanfei Tao, Shuyu Xie, Fanfan Xu, Yanxin Wang, Dongmei Chen, Yuanhu Pan, Lingli Huang, Dapeng Peng, Xu Wang, Zonghui Yuan
Ochratoxin A (OTA) is a widespread mycotoxin commonly found as a corn contaminant. It has been shown to be nephrotoxic, hepatotoxic, teratogenic and immunotoxic to several species of animals and to cause kidney and liver tumors in mice and rats. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for OTA-induced toxicity as well as its metabolism. The present review shows that studies have been carried out for decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of OTA treatment and have correlated them with various types of OTA toxicity, indicating that oxidative stress plays critical roles in the toxicity of OTA. The major metabolic pathways of OTA are hydrolysis and a small percentage of absorbed OTA is hydroxylated. CYP450, carboxypeptidase A, trypsin, α-chymotrypsin and cathepsin have been shown to be able to degrade OTA. Most metabolites of OTA are less toxic than OTA except OP-OTA. Further understanding of the role of oxidative stress in OTA-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of the metabolism and metabolic enzymes of OTA. The present review might contribute to reveal the oxidative stress-induced toxicity of OTA and help to protect against its oxidative damage.
Essential roles of Akt/Snail pathway in microcystin-LR-induced tight junction toxicity in Sertoli cell Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-04 Yuan Zhou, Xiao Geng, Yu Chen, Hao Shi, Yan Yang, Chan Zhu, Guang Yu, Zongxiang Tang
Microcystin (MC)-LR is a cyclic heptapeptide that acts as a potent reproductive system toxin. However, the underlying pathways of MCLR-induced reproductive system toxicity have not been well elucidated. The blood-testis barrier is mainly constituted by tight junctions (TJs) between adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. The present study was designed to investigate changes in TJs and the underlying pathway in MC-LR-induced TJs toxicity in Sertoli cell. In our study, the transepithelial electrical resistance (TER) value was decreased in a dose dependent manner due to the markers of TJs occludin, claudin and zonula occludens-1 (ZO-1) expression decline. MC-LR is shown to induce cytotoxicity by inhibiting protein phosphatase 2A (PP2A) activity. Our results also showed that the PP2A activity presented a dose-dependent decline. Moreover, MC-LR stimulated protein expression of snail by Akt/GSK-3β activation. The activated Akt/GSK-3β and snail signaling pathway largely accounted for MC-LRinduced TJs toxicity, which could be partially reversed by snail siRNA interference or AKT chemical inhibitor in TM4 cells. These findings indicated that MC-LR inhibit the protein expression of TJs, and the activation of Akt/Snail signaling pathways due to PP2A inhibition is proposed to participate in this process.
A comparative study of human IgE binding to proteins of a genetically modified (GM) soybean and six non-GM soybeans grown in multiple locations Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-04 Mei Lu, Yuan Jin, Barbara Ballmer-Weber, Richard E. Goodman
Discrimination of three Siegesbeckiae Herba species using UPLC-QTOF/MS-based metabolomics approach Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-03 Hong-Xun Tao, Wei Xiong, Guan-Ding Zhao, Yu Peng, Zhang-Feng Zhong, Liang Xu, Ran Duan, Karl W.K. Tsim, Hua Yu, Yi-Tao Wang
The plant origin is one of the most important factors for the quality control of traditional Chinese medicines (TCMs) and highly affected on their safety and effectiveness in clinical applications. Multi-origin has been widely observed for many TCMs. Siegesbeckiae Herba (SH) is a traditional anti-rheumatic TCM which is originated from the plants of Siegesbeckia pubescens Makino (SP), S. orientalis L. (SO), and S. glabrescens Makino (SG). In the present study, an UPLC-QTOF/MS method were validated and successfully applied for the determination of the chemical profiles in the three SH species. The data were statistical analyzed with the OPLS-DA analysis and One-Way ANOVA F-test. Obvious differences in chemistry were observed in different SH species and 40 components were identified. Finally, 6 components were selected as potential chemical markers for the discrimination of SP, SO and SG based on the characteristic distribution in individual SH species.
Anti-proliferative activity of biochanin A in human osteosarcoma cells via mitochondrial-involved apoptosis Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-03 Yen-Nien Hsu, Huey-Wen Shyu, Tsui-Wen Hu, Jou-Pei Yeh, Ya-Wen Lin, Ling-Yi Lee, Yao-Tsung Yeh, Hong-Ying Dai, Daw-Shyong Perng, Shu-Hui Su, Yu-Hsuan Huang, Shu-Jem Su
Biochanin A is a major isoflavone in red clover and a potent chemopreventive agent against cancer. However, the effects of biochanin A on human osteosarcoma cells have never been clarified. This study investigated the anti-proliferative potential of biochanin A in osteosarcoma cells. The results indicate that biochanin A inhibited cell growth and colony formation in a dose-dependent manner with a minimal toxicity to normal cells. The combination of doxorubicin and biochanin A could synergistically inhibit osteosarcoma cell growth. The cytotoxic effect of biochanin A via the induction of apoptosis as evidenced by formation of apoptotic bodies, externalization of phosphatidylserine, accumulation of sub-G1 phase cells, caspase 3 activation, and cleavage of PARP. Apoptosis was associated with loss of the mitochondrial membrane potential, release of cytochrome c, caspase 9 activation, increased Bax expression, and reduced Bcl-2 and Bcl-XL expression. Pre-treatment with a caspase-9 specific inhibitor (Z-LEHD-FMK) partially attenuated cell death, suggesting involvement of the intrinsic mitochondrial apoptotic cascade. However, pre-treatment with the JNK inhibitor SP600125, the MEK inhibitor PD-98059, and the p38 MAPK inhibitor SB203580 or the antioxidants vitamin E, N-acetylcysteine, and glutathione failed to prevent biochanin A-induced cell death. Our results suggest that biochanin A inhibits cell growth and induces apoptosis in osteosarcoma cells by triggering activation of the intrinsic mitochondrial pathway and caspase-9 and -3 and increasing the Bax: Bcl-2/Bcl-XL ratio.
Cytochrome P450 4A11 inhibition assays based on characterization of lauric acid metabolites Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-03 Yeon Jung Choi, Yuanyuan Zhou, Ji-Yoon Lee, Chang Seon Ryu, Young Ho Kim, Kiho Lee, Sang Kyum Kim
The protective effect of diallyl trisulfide on cytopenia induced by benzene through modulating benzene metabolism Food Chem. Toxicol. (IF 3.778) Pub Date : 2018-01-02 Wenting Han, Shuo Wang, Ming Li, Lulu Jiang, Xujing Wang, Keqin Xie
Assessment of mutagenic, recombinogenic and carcinogenic potential of titanium dioxide nanocristals in somatic cells of Drosophila melanogaster Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-30 Maria Paula Carvalho Naves, Cássio Resende de Morais, Anielle Christine Almeida Silva, Noelio Oliveira Dantas, Mário Antônio Spanó, Alexandre Azenha Alves de Rezende
Nanoparticles have been widely used in several sectors and their long-term effect on the body and environment remains unknown. To evaluate the mutagenic, recombinogenic and carcinogenic potential of 11 nm titanium dioxide nanocrystals (TiO2 NCs), the Somatic Mutation and Recombination Test (SMART) and the Test for Detection of Epithelial Tumors Clones (Warts-Wts) were used, both in Drosophila melanogaster. Third-instar larvae (72 + 4 h), obtained in both tests, were treated with different concentrations of TiO2 NCs ranging from 6.25 to 100 mM. Ultrapure water and urethane were used as negative and positive controls, respectively. At ST cross, all concentrations of TiO2 NCs showed a significant increase in the frequencies of mutant spots, demonstrating higher recombination rates. At the HB cross, only the 50 mM concentration showed a negative result. In the Wts Test, all used concentrations were carcinogenic, except for the 100 mM one, which was toxic. No relationship was demonstrated between the used concentrations and the obtained responses. There was no interference of the cytochrome P450 enzyme complex in the induction of mutant spots.
Mixture effects of two plant protection products in liver cell lines Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-30 E. Zahn, J. Wolfrum, C. Knebel, T. Heise, F. Weiß, O. Poetz, P. Marx-Stoelting, S. Rieke
Pesticide products contain one or more active substances as well as adjuvants, which are added for example as solvents or antioxidants. Nevertheless, only the active substances are evaluated with a comprehensive battery of mammalian toxicity tests. However, in some cases mixture effects of active substances and adjuvants may occur, leading to increased toxicity of the products. To address this issue, we investigated effects of active substances with known hepatotoxicity and two commonly used fungicides: Priori Xtra® and Adexar®. For this purpose, respective active substances individually and in combination as well as the products were applied to two human hepatoma cell lines (HepaRG and HepG2) in a broad dose range. The results of cytotoxicity analysis, nuclear receptor transactivation (AhR, CAR, PXR), mRNA and protein expression of xenobiotic metabolizing enzymes (CYP1A1, CYP2B6 and CYP3A4) allow the conclusion that active substances and plant protection products differ in terms of their in vitro toxicity. The products activate AhR, while the individual active substances as well as the combination of the active substances have no or only minor effects. The present results support the hypothesis that plant protection products may have a modified toxicity as compared to active substances alone, consequently requiring more comprehensive testing.
Rapid screening and multi-toxin profile confirmation of tetrodotoxins and analogues in human body fluids derived from a puffer fish poisoning incident in New Caledonia Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-30 Maria Rambla-Alegre, Sandra Leonardo, Yann Barguil, Cintia Flores, Josep Caixach, Katrina Campbell, Christopher T. Elliott, Claude Maillaud, Michael J. Boundy, D. Tim Harwood, Mònica Campàs, Jorge Diogène
In August 2014, a puffer fish poisoning incidence resulting in one fatality was reported in New Caledonia. Although tetrodotoxin (TTX) intoxication was established from the patients' signs and symptoms, the determination of TTX in the patient's urine, serum or plasma is essential to confirm the clinical diagnosis. To provide a simple cost-effective rapid screening tool for clinical analysis, a maleimide-based enzyme-linked immunosorbent assay (mELISA) adapted for the determination of TTX contents in human body fluids was assessed. The mELISA was applied to the analysis of urine samples from two patients and a response for the presence of TTX and/or structurally similar analogues was detected in all samples. The analysis by LC-MS/MS confirmed the presence of TTX but also TTX analogues (4-epiTTX, 4,9-anhydroTTX and 5,6,11-trideoxyTTX) in the urine. A change in the multi-toxin profile in the urine based on time following consumption was observed. LC-MS/MS analysis of serum and plasma samples also revealed the presence of TTX (32.9 ng/mL) and 5,6,11-trideoxyTTX (374.6 ng/mL) in the post-mortem plasma. The results provide for the first time the TTX multi-toxin profile of human samples from a puffer fish intoxication and clearly demonstrate the implication of TTX as the causative agent of the reported intoxication case.
Evaluation of the antioxidant and gastroprotective activity and HPLC analysis of the hydroalcoholic extract of Tocoyena formosa leaves (Cham. & Schlecht) K. Schum Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-30 Francisco Rafael Alves Santana Cesário, Thaís Rodrigues de Albuquerque, Bruno Anderson Fernandes da Silva, Giovana Mendes de Lacerda, Lindaiane Bezerra Rodrigues, Anita Oliveira Brito Pereira Bezerra Martins, Lucindo Jose Quintans-Júnior, Jackson Roberto Guedes da Silva Almeida, Mariana Lima Vale, Henrique Douglas Melo Coutinho, Irwin Rose Alencar de Menezes
The peptic ulcer is a gastric disorder that affects millions of people and yet they cause many side effects. In this sense, natural products represent an important alternative to the discovery of compounds with gastroprotective activity. The present work has as its objective to evaluate the antioxidant and gastroprotective activity of the Hydroalcoholic Extract of Leaves from Tocoyena formosa (Cham. & Schlecht.) K. Schum (HELTF), this being much emphasized in traditional medicine for inflammatory morbidities and gastric symptoms. For the evaluation of the antioxidant activity, FRAP and DPPH tests were carried out, and for the evaluation of the gastroprotective activity, gastric lesion induction by ethanol, acidified ethanol, indomethacin and physical barrier tests were used. Antioxidant assay of HELTF revealed an EC50 of 558.66 μM FeSO4/g and IC50 of 189.78 μg/ml for FRAP and DPPH respectively. In gastroprotective, in ethanol model, all the doses presented significant activity in comparison to controls, however, in the gastric lesion induction test by acidified ethanol and indomethacin, only the dose of 200 mg/kg presented with significance. In the physical barrier test presented evidence that protection by the formation of a protective layer associated with mucus. Concluded, therefore, that HELTF possesses antioxidant and significate gastroprotective activity.
Detoxification of trichothecene mycotoxins by a novel bacterium, Eggerthella sp. DII-9 Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-30 Xiaojuan Gao, Peiqiang Mu, Jikai Wen, Yu Sun, Qingmei Chen, Yiqun Deng
Trichothecene mycotoxins are a group of structurally related sesquiterpenoid metabolites produced by multiple Fusarium species that often contaminate cereals and threaten human and animal health. The basic structure of this mycotoxin group is a characteristic 12, 13-epoxide group, which is considered an essential functional group for toxicity. In this study, using trichothecene mycotoxin deoxynivalenol (DON) as a representative substrate, we identified a novel trichothecene deepoxidation bacterium, Eggerthella sp. DII-9 (DII-9), from chicken intestines. DII-9 can grow and transform DON over abroad range of temperatures (20–45 °C) and pH values (5–10), suggesting the possibility of developing promising future applications as feed additives. Substrate specificity analysis showed that DII-9 is capable of promoting the deepoxidation of DON, HT-2, T-2 triol and T-2 tetraol. To explore the molecular mechanisms of the de-epoxidation of trichothecenes, the complete genome of DII-9 was sequenced and characterized. Altogether, a novel detoxification bacterium for trichothecene mycotoxins was identified and characterized.
Status of microbial based cleaning products in statutory regulations and ecolabelling in Europe, the USA, and Canada Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-29 Armin Spök, George Arvanitakis, Gwendolyn McClung
Cleaning products containing living microorganisms as active ingredients are increasingly being used in household, professional and industrial cleaning applications. Microorganisms can degrade soiling associated with dirt, food residues, and grease by enzymatic and metabolic action and out-compete microorganisms associated with odor problems. Their potential for odor control seems to result in a competitive advantage over conventional chemically-based cleaning products. Moreover, producers of microbial-based cleaning products (MBCPs) claim that their products are less harmful to the environment. These promising prospects have triggered interest from consumer and environmental organizations, professional users, and regulators in understanding if there are also possible negative health and environmental impacts which require attention and how the safety of these products is ensured. Unfortunately, there is little information on these issues in the public domain. Moreover, regulatory oversight in Europe is essentially limited to pathogenic properties in the context of worker protection. Canada, in contrast, has a regulatory framework in place to assess risks to human health and the environment from the manufacture, import and/or use of new microorganisms contained in MBCPs. In the absence of mandatory standards, safety assessment and hygienic practices seem to vary considerably across companies. Recently developed ecolabelling standards are – for the time being - the only option for transparent compliance to minimum standards in terms of safety as well as assessments of manufacturer information by third parties. These standards highlight in particular the need for precise taxonomic information for assessing the pathogenic properties and the need to ensure the absence of potentially harmful microorganisms as contaminants. Ecolabelling standards are, however, voluntary and do not cover all relevant safety issues. In order to develop a more comprehensive set of mandatory standards for health and safety, a number of areas would benefit from further research (e.g. the role in plant pathogenicity and other environmental properties of the microorganisms used; the relevance of chronic exposure to dusts and aerosols containing vegetative cells and spores; the relevance of strains which belong to species known to include opportunistic pathogens and possible hazards for particularly sensitive risk groups). Improved knowledge in these areas will contribute to a predictable level of product safety.
Is comfrey root more than toxic pyrrolizidine alkaloids? Salvianolic acids among antioxidant polyphenols in comfrey (Symphytum officinale L.) roots Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-28 Adriana Trifan, Sebastian E.W. Opitz, Roland Josuran, Andreas Grubelnik, Nils Esslinger, Samuel Peter, Sarah Bräm, Nadja Meier, Evelyn Wolfram
Comfrey root preparations are used for the external treatment of joint distortions and myalgia, due to its analgesic and anti-inflammatory properties. Up to date, key activity-determining constituents of comfrey root extracts have not been completely elucidated. Therefore, we applied different approaches to further characterize a comfrey root extract (65% ethanol). The phenolic profile of comfrey root sample was characterized by HPLC-DAD-QTOF-MS/MS. Rosmarinic acid was identified as main phenolic constituent (7.55 mg/g extract). Moreover, trimers and tetramers of caffeic acid (isomers of salvianolic acid A, B and C) were identified and quantified for the first time in comfrey root. In addition, pyrrolizidine alkaloids were evaluated by HPLC-QQQ-MS/MS and acetylintermedine, acetyllycopsamine and their N-oxides were determined as major pyrrolizidine alkaloids in the comfrey root sample. Lastly, the antioxidant activity was determined using four assays: DPPH and ABTS radicals scavenging assays, reducing power assay and 15-lipoxygenase inhibition assay. Comfrey root extract exhibited significant antioxidant activities when compared to known antioxidants. Thus, comfrey root is an important source of phenolic compounds endowed with antioxidant activity which may contribute to the overall bioactivity of Symphytum preparations.
Essential oil of Citrus lumia Risso: Phytochemical profile, antioxidant properties and activity on the central nervous system. Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-28 Antonella Smeriglio, Susanna Alloisio, Francesco Maria Raimondo, Marcella Denaro, Jianbo Xiao, Laura Cornara, Domenico Trombetta
Chemical findings and in vitro biological studies to uphold the use of Ficus exasperata Vahl leaf and stem bark Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-27 Didier G. Mouho, Andreia P. Oliveira, Charles Guillaume Kodjo, Patrícia Valentão, Angel Gil-Izquierdo, Paula B. Andrade, Zana Adama Ouattara, Yves-Alain Bekro, Federico Ferreres
Ficus exasperata Vahl, commonly known as sandpaper, is a terrestrial Afro-tropical tree used in popular medicine. Despite the existence of some works on the biological activities of this species, its chemical composition is still poorly known. The aim of this study was to extend the knowledge on the phytochemistry and biological properties of this species. Aqueous extracts from F. exasperata leaves and stem bark were analysed. Thirty-one phenolic compounds, comprising cinnamoyl derivatives, flavonoid-O-glycosides, flavonoid-mono-C-glycosides, flavonoid-di-C-glycosides and one furanocoumarin, were determined by HPLC–DAD–ESI/MSn and UPLC-ESI-QTOF-MS, 26 of them being reported for the first time in this species. The profile of organic acids, characterized by HPLC-UV, was also reported for the first time. The best radical scavenging activity was observed for the aqueous extract from leaves (IC50 values of 222.5, 510.0 and 50.0 μg/mL against DPPH•, •NO and O2•-, respectively). In addition, both aqueous extracts of the leaves and stem bark displayed a weak effect on α-amylase, and no cytotoxicity against gastric adenocarcinoma cell line, AGS. This study contributes to the valorisation of these vegetal materials, which may have application in functional foods and/or nutraceuticals.
Toxicity and toxicokinetic study of RPh201 in Sprague-Dawley rats Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-27 Yuval Ramot, Zadik Hazan, Andre Lucassen, Konstantin Adamsky, D.P. Santhosh Kumar, S.K. Vijayasarathi, H. Krishnappa, Madhav Singh Seervi, Abraham Nyska
Mastic gum is used for health products and in the food industry, and is being tested for several clinical indications. Nevertheless, information on its safety is scarce. Our aim was to test the local and systemic toxicity of RPh201, a botanical extract of gum mastic, and to assess the toxicokinetic profile of the mastic gum constituents masticadienonic acid (MDA) and isomasticadienonic acid (IMDA). 340 Sprague-Dawley rats were administered twice weekly subcutaneously with placebo or different doses of RPh201 for 6 months with an interim group at 3 months and a 4-week recovery group. No systemic toxicity was observed with RPh201. Local injection site reactions were observed in all animals, with comparable severity and frequency in the placebo and high dose groups. However, given the relative increase in tissue reaction in the high dose group, these changes were attributed to RPh201 administration. Nevertheless, considering the minor local irritation effects and clear trend for reversibility, the effects were not judged to be adverse. The toxicokinetic study revealed that the MDA and IMDA exposure increased with dose and the increase was supra-proportional on all days. This study supports a “no observed adverse effect level” (NOAEL) of 300 mg/kg body weight in Sprague-Dawley rats.
Do flavanols-rich natural products relieve obesity-related insulin resistance? Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-27 Ayse Basak Engin, Aristidis M. Tsatsakis, Dimitris Tsoukalas, Atilla Engin
Growing evidence support that insulin resistance may occur as a severe problem due to chronic energetic overfeeding and subsequent obesity. When an abundance of glucose and saturated fat enter the cell, impaired blood flow, hypoxia, inflammation and macrophage infiltration in obese adipose tissue may induce oxidative stress and insulin resistance. Excessive circulating saturated fatty acids ectopically accumulate in insulin-sensitive tissues and impair insulin action. In this context, excessive hepatic lipid accumulation may play a central, pathogenic role in insulin resistance. It is thought that dietary polyphenols may ameliorate obesity-related insulin resistance by attenuating inflammatory responses and oxidative stress. The most often occurring natural polyphenolic compounds are flavonoids. In this review, the possible mechanistic effect of flavonoid-rich natural products on insulin resistance-related metabolic pathways is discussed. Polyphenol intake can prevent high-fat-diet-induced insulin resistance via cell surface G protein-coupled estrogen receptors by upregulating the expression of related genes, and their pathways, which are responsible for the insulin sensitivity.
The frequently occurring components of essential oils beta elemene and R-limonene alter expression of dprE1 and clgR genes of Mycobacterium tuberculosis H37Ra Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-27 Rafal Sawicki, Elwira Sieniawska, Marta Swatko-Ossor, Joanna Golus, Grazyna Ginalska
In the past few years, there has been a significant increase in detection of drug resistant strains of Mycobacterium tuberculosis. Search for new antimycobacterial drugs brought natural sources with their chemical diversity in focus. Especially essential oils, produced by plants also for toxic effect, are reservoir of potentially antitubercular compounds. In the present work, we exposed M. tuberculosis H37Ra ATCC 25177 strain to some terpenes commonly occurring in essential oils. Gene expression profiling was used to explore possible influence of these compounds on stress sensing and envelope preserving function. Expression of two genes dprE1 involved in cell wall synthesis and clgR responsible for regulation of cell membrane preservation was investigated. We report that two out of five tested compounds: β-elemene and R-limonene alter expression of dprE1 and clgR genes. These findings indicate various mechanisms of action of essential oils compounds on M. tuberculosis. Especially the clgR expression seemed to be the perfect marker of stress sensing and envelope preserving systems status.
Activity of MPF and expression of its related genes in mouse MI oocytes exposed to cadmium Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-26 Jin Liu, Xiaoli Lu, Wenxiang Wang, Jianlin Zhu, Yuchen Li, Lingfeng Luo, Wenchang Zhangb
Platycodon grandiflorum-derived saponin attenuates the eccentric exercise-induced muscle damage Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-26 Yong-An Kim, Suck-Hoon Oh, Gi-Ho Lee, Pham Thi Hoa, Sun Woo Jin, Young Chul Chung, Young Chun Lee, Hye-Gwang Jeong
Platycodon grandiflorum contains triterpenoid saponins, such as platycodin D and platyconic acid A, and acts as a multifold nutritious compound. Our previous research demonstrated that Platycodon grandiflorum-derived saponin (PS) improves high-fat diet-induced non-alcoholic steatohepatitis and inhibits osteoclast differentiation. The pivotal effects of PS on inflammatory mechanism were suppressed NF-κB and matrix metalloproteinase (MMPs). However, the effects of PS on skeletal muscle damage remain unknown. Therefore, we investigated whether PS protects against eccentric exercise-induced muscle damage. A significant reduction in eccentric exercise-induced muscle damage area and muscle damage related to the level of NF-κB p65 by PS was associated with the downregulation of ERK/p38/SMAD signaling. Eccentric exercise caused muscle damage by increasing the serum lactate dehydrogenase (LDH), creatinine kinase (CK) and C-related protein level. The serum LDH, CK and C-related protein level was significantly lower in the PS supplementation group compared with the control group. Moreover, PS was inhibited MMP-1, MMP-2 and MMP-9. PS protects against eccentric exercise-induced muscle damage. Together, these results provide a novel perspective on the biological function of PS against muscle damage.
Chemical characterization, antioxidant, genotoxic and in vitro cytotoxic activity assessment of Juniperus communis var. saxatilis Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-26 Bojana Vasilijević, Jelena Knežević-Vukčević, Dragana Mitić-Ćulafić, Dejan Orčić, Marina Francišković, Tatjana Srdic-Rajic, Marina Jovanović, Biljana Nikolić
Skin sensitisation quantitative risk assessment (QRA) based on aggregate dermal exposure to methylisothiazolinone in personal care and household cleaning products Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-25 J. Ezendam, B.G.H. Bokkers, W. Bil, J.E. Delmaar
Contact allergy to preservatives is an important public health problem. Ideally, new substances should be evaluated for the risk on skin sensitization before market entry, for example by using a quantitative risk assessment (QRA) as developed for fragrances. As a proof-of-concept, this QRA was applied to the preservative methylisothiazolinone (MI), a common cause of contact allergy. MI is used in different consumer products, including personal care products (PCPs) and household cleaning products (HCPs). Aggregate exposure to MI in PCPs and HCPs was therefore assessed with the Probabilistic Aggregated Consumer Exposure Model (PACEM). Two exposure scenarios were evaluated: scenario 1 calculated aggregate exposure on actual MI product concentrations before the restricted use in PCPs and scenario 2 calculated aggregate exposure using the restrictions for MI in PCPs. The QRA for MI showed that in scenarios 1 and 2, the proportion of the population at risk for skin sensitisation is 0.7% and 0.5%, respectively. The restricted use of MI in PCPs does not seem very effective in lowering the risk on skin sensitization. To conclude, it is important to consider aggregate exposure from the most important consumer products into consideration in the risk assessment.
Grapefruit and its biomedical, antigenotoxic and chemopreventive properties Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-25 José Melesio Cristóbal-Luna, Isela Álvarez-González, Eduardo Madrigal-Bujaidar, Germán Chamorro Cevallos
Grapefruit (Citrus paradisi Mcfad) is a perenifolium tree 5–6 m high with a fruit of about 15 cm in diameter, protected by the peel we can find about 11–14 segments (carpels), each of which is surrounded by a membrane and each containing the juice sacs, as well as the seeds. The fruit is made up of numerous compounds, and is known to have nutritive value because of the presence of various vitamins and minerals, among other chemicals. The fruit is also used in the field of gastronomy. Information has been accumulated regarding the participation of the fruit structures in a variety of biomedical, antigenotoxic and chemopreventive effects, surely related with the presence of the numerous chemicals that have been determined to constitute the fruit. Such studies have been carried out in different in vitro and in vivo experimental models, and in a few human assays. The information published so far has shown interesting results, therefore, the aims of the present review are to initially examine the main characteristics of the fruit, followed by systematization of the acquired knowledge concerning the biomedical, antigenotoxic and chemopreventive effects produced by the three main structures of the fruit: peel, seed, and pulp.
Are by-products from beeswax recycling process a new promising source of bioactive compounds with biomedical properties? Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-25 Francesca Giampieri, José L. Quiles, Francisco J. Orantes-Bermejo, Massimiliano Gasparrini, Tamara Y. Forbes-Hernandez, Cristina Sánchez-González, Juan Llopis, Lorenzo Rivas-García, Sadia Afrin, Alfonso Varela-López, Danila Cianciosi, Patricia Reboredo-Rodriguez, Cristina Torres Fernández-Piñar, Ruben Calderón Iglesias, Roberto Ruiz, Silvia Aparicio, Jorge Crespo, Luis Dzul Lopez, Jianbo Xiao, Maurizio Battino
Nitrosative deamination of 2′-deoxyguanosine and DNA by nitrite, and antinitrosating activity of β-carboline alkaloids and antioxidants Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-22 Tomás Herraiz, Juan Galisteo
Evaluation of antioxidant activities of ethanol extract from Ligusticum subjected to in-vitro gastrointestinal digestion Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-21 Huifang Ge, Yazhen Chen, Jicheng Chen, Jingjing Tian, Xiaofeng Liang, Lei Chen
The Rhizome of Ligusticum chuanxiong Hort, a traditional Chinese medicine, is widely used to treat cardiovascular diseases and attenuate oxidative stress. The main bioactive compounds including tetramethylpyrazine (TMP), polyphenols, ferulic acid have been reported to be responsible for these effects. This study was to evaluate the influence of Ligusticum chuanxiong extraction (LCE) in mimic gastrointestinal tract on antioxidant activity. The effects of gastric digestion group metabolic liquid on free radical scavenging followed as DPPH > ·O2− > ·OH, while the clearance effects of intestine digestion group expressed as ·O2−> ·OH > DPPH. Furthermore, the digested extraction promoted lower cellular antioxidant activity (CAA) with dose-response correlations. Gastrointestinal digestion increased the release of bound ferulic acids and polyphenols. Content of ferulic acid in gastric and intestinal metabolic solution increased from 6.07 mg/g to 9.33 mg/g and 14.17 mg/g. The free phenolic before and after digestion were 177.38 mg/g, 179.69 mg/g and 194.99 mg/g, respectively. The simulated gastrointestinal digestion of LCE promoted a significant increase in the free phenolic acids content, antioxidant activity and CAA.
Gypenosides protect retinal pigment epithelium cells from oxidative stress Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-21 Reem Hasaballah Alhasani, Lincoln Biswas, Ali Mohammed Tohari, Xinzhi Zhou, James Reilly, Jian-Feng He, Xinhua Shu
Toxicity reduction of ochratoxin A by lactic acid bacteria Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-20 C. Luz, J. Ferrer, J. Mañes, G. Meca
Ochratoxin A (OTA) is a mycotoxin produced by the metabolism of fungus belonging to the genus Aspergillus and Penicillium. In this paper we report, the capacity of different cultures of lactic acid bacteria (LAB) to degrade OTA present in MRS broth at both pH 3.5 and 6.5. A study of OTA reduction during gastrointestinal digestion carried out with the LAB was also performed. Taking into account the two reduction mechanisms of OTA studied in this work as the enzymatic one and the adsorption on the cell wall, as well as at pH 3.5 and 6.5 the reduction values of OTA were in a range of 30–99%, being the strains with greater reduction (97% and 95%) Lb. rhamnosus CECT 278T and Lb. plantarum CECT 749 respectively. In the experiments carried out digesting the OTA in MRS medium with LAB, the highest bioaccessibility reduction was observed by the strain of Lb. johnsonii CECT 289, showing a mean reduction around all the gastrointestinal digestion process of 97.4%. The mass spectrometry associated to the linear ion trap method identified ochratoxin alpha (OTα) m/z = 256.1 and phenylalanine (Phe) m/z = 166.1 as the major metabolites of OTA degradation in LAB cultures.
Dietary cumulative acute risk assessment of organophosphorus, carbamates and pyrethroids insecticides for the Brazilian population Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-20 Andreia Nunes Oliveira Jardim, Alessandra Page Brito, Gerda van Donkersgoed, Polly E. Boon, Eloisa Dutra Caldas
Cumulative acute dietary risk assessments of organophosphorus (OPs), carbamates (CBs) and pyrethroids (PYs) were conducted for the Brazilian population. Residue data for 30786 samples of 30 foods were obtained from two national monitoring programs and one University laboratory, and consumption data from a national survey conducted among persons 10 years or older. Acephate and methamidophos were used as index compounds (IC) for OPs, oxamyl for CBs and deltamethrin for PYs. Exposures were estimated using the Monte Carlo Risk Assessment (MCRA 8.2) software. Orange and orange juice (mainly containing methidathion), pasta and salted bread (mainly pirimiphos-methyl) contributed most to the OPs intake. Rice accounted for 80% of the CBs intake (teenagers), mainly due to aldicarb. Pasta, salted bread and beans contributed most to the PYs intake (9–14%), mainly due to bifenthrin. The intake did not exceed the ARfD at the 99.9th percentile for OPs, CBs and PYs, and the risks from the exposure were not considered of health concern. When food consumption data become available for children under age 10, studies in the cumulative exposure should be conducted, as this age group is the most critical among the population, mainly due to their higher consumption per kg body weight.
Pirfenidone protects against paraquat-induced lung injury and fibrosis in mice by modulation of inflammation, oxidative stress, and gene expression Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-19 Fateme Pourgholamhosein, Rokhsana Rasooli, Mostafa Pournamdari, Leyla Pourgholi, Mitra Samareh-Fekri, Mahmoud Ghazi-Khansari, Maryam Iranpour, Hamid-Reza Poursalehi, Mahmoud-Reza Heidari, Ali Mandegary
Development and use of microbial-based cleaning products (MBCPs): Current issues and knowledge gaps Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-19 George Arvanitakis, Robin Temmerman, Armin Spök
Cleaning products containing microbes as active ingredients are becoming increasingly prevalent as an alternative to chemical-based cleaning products. These microbial-based cleaning products (MBCPs) are being used in domestic and commercial settings (i.e., households and businesses) and institutional settings (e.g., hospitals, schools, etc.), in a variety of cleaning activities (hard surface cleaning, odour control, degreasing, septic tank treatments, etc.). They are typically described as “environmentally friendly” and “non-toxic”. Publicly available information sources (scientific literature, patent databases, commercial websites) were searched for information on microbial species contained in MBCPs, their mode of action, cleaning applications in which they are used, and their potential impacts on human health and the environment. Although information was found providing a broad indication of microbial genera/species used, information on specific species/strains and quantities produced and sold is generally lacking. This makes it difficult to conduct a meaningful examination of any risks to human health and the environment from the production and use of MBCPs and to determine how effective current policies and regulatory frameworks are in addressing these issues. These and other challenges were addressed at an international workshop in Ottawa, Canada in June 2013 by a number of stakeholders, including industry, government, academic and non-governmental organizations.
Allergens of permanent hair dyes induces epidermal damage, skin barrier loss and IL-1 α increase in epidermal in vitro model Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-19 Thalita Boldrin Zanoni, Tatiana Nascimento Pedrosa, Carolina Motter Catarino, Sander W. Spiekstra, Danielle Palma de Oliveira, Gertjan Den Hartog, Aalt Bast, Geja Hagemann, Susan Gibbs, Silvia Berlanga de Moraes Barros, Silvya Stuchi Maria–Engler
Allergic and irritant skin reactions caused by topical exposure to permanent hair dyes are a common problem. For regulatory and ethnical purposes, it is required to perform chemical safety assessment following the replacement, reduction, and refinement of animal testing (3Rs). Permanent hair dyes are formed by a mixture of ingredients that vary from low to extreme skin sensitizing potency and that inter-react to form unknown by-products. Because of the complex reaction, this cytotoxic mechanism has not yet been elucidated and is the subject of this study. Here, we topically exposed p-phenylenediamine (PPD), Resorcinol (RES), H2O2 alone or as a mixture to RhE and evaluated parameters related to skin irritation such as epidermal viability, keratinocytes damage, barrier loss and IL-1 α. Our data indicates that ingredients tested alone did not lead to an increase of cytotoxic parameters related to skin irritation. However, when the mixture of PPD/H2O2/RES and PPD/H2O2 was applied to the RhE, some of the parameters such as morphological changes including the presence of apoptotic cells, barrier loss and increased IL- 1 α release were observed. The results indicate that the mixture of ingredients used in permanent hair dyes have an irritant effect in RhE while the ingredients alone not.
Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A: Mechanism of hepatotoxicity and biomarker discovery Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-18 Faezeh Vahdati Hassani, Khalil Abnous, Soghra Mehri, Amirhossein Jafarian, Ruth Birner-Gruenberger, Rezvan Yazdian Robati, Hossein Hosseinzadeh
Trace determination of carbamate pesticides in medicinal plants by a fluorescent technique Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-18 Jin-Chao Wei, Bin Wei, Wu Yang, Cheng-Wei He, Huan-Xing Su, Jian-Bo Wan, Peng Li, Yi-Tao Wang
Genotoxicity and antioxidant activity of five Agrimonia and Filipendula species plant extracts evaluated by comet and micronucleus assays in human lymphocytes and Ames Salmonella/microsome test Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-18 Milda Pukalskienė, Gražina Slapšytė, Veronika Dedonytė, Juozas Rimantas Lazutka, Jūratė Mierauskienė, Petras Rimantas Venskutonis
The species of Agrimonia and Filipendula have been traditionally used in folk medicine as anti-inflammatory herbs. This study extends the knowledge on bioactivities of F. palmata, A. eupatoria, A. procera, F. ulmaria and F. vulgaris by comprehensive characterization of their methanolic extracts. Antioxidant properties of extracts were evaluated by DPPH• (2,2-diphenyl-1-picrylhydrazyl), ABTS•+ 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) scavenging and oxygen radical absorbance capacities (ORAC). Genotoxicity of extracts was tested using alkaline single-cell gel electrophoresis (comet) and cytokinesis-block micronucleus assays in human lymphocytes in vitro and the Ames Salmonella/microsome test. All investigated Agrimonia and Filipendula extracts possessed strong antioxidant activity, which was comparable with that of a standard antioxidant trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Thirty five compounds belonging to the classes of phenolic acids, flavonoids, phenylpropanoids and ellagitanins were detected by ultra-performance liquid chromatography – mass spectrometry (UPLC-Q-TOF-MS). Agrimonia and Filipendula extracts induced an increase in a DNA damage in the comet assay expressed as mean percentage of DNA in the comet tail. However, these extracts did not produce reverse mutation in bacterial cells in the Ames test and were not genotoxic in the micronucleus test. However, a slight though significant decrease of nuclear division index values was determined. In general, this study proved that Agrimonia and Filipendula species are a good source of bioactive compounds; their extracts may be classified as non-mutagenic and non-clastogenic in vitro under conditions of the current study. Consequently, the plants may be a promising material for nutraceuticals and natural medicines.
Enhancement of colon carcinogenesis by the combination of indole-3 carbinol and synbiotics in hemin-fed rats Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-18 Nelci A. de Moura, Brunno F.R. Caetano, Leonardo N. de Moraes, Robson F. Carvalho, Maria A.M. Rodrigues, Luis F. Barbisan
Molecular chemotherapeutic potential of butein: A concise review Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-16 Rajapaksha Gedara Prasad Tharanga Jayasooriya, Ilandarage Menu Neelaka Molagoda, Cheol Park, Jin-Woo Jeong, Yung Hyun Choi, Dong-Oh Moon, Mun-Ock Kim, Gi-Young Kim
Butein is a biologically active flavonoid isolated from the bark of Rhus verniciflua Stokes, which is known to have therapeutic potential against various cancers. Notably, butein inhibits cancer cell growth by inducing G2/M phase arrest and apoptosis. Butein-induced G2/M phase arrest is associated with increased phosphorylation of ataxia telangiectasia mutated (ATM) and Chk1/2, and consequently, with reduced cdc25C levels. In addition, butein-induced apoptosis is mediated through the activation of caspase-3, which is associated with changes in the expression of Bcl-2 and Bax proteins. Intriguingly, butein sensitizes cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via ERK-mediated Sp1 activation, which promotes the transcription of specific death receptor 5. Butein also inhibits the migration and invasion of human cancer cells by suppressing nuclear factor-κB- and extracellular signal-regulated kinases 1/2-mediated expression of matrix metalloproteinase-9 and vascular endothelial growth factor. Additionally, butein downregulates the expression of human telomerase reverse transcriptase and causes a concomitant decrease in telomerase activity. These findings provide the basis for the pharmaceutical development of butein. The aim of this review is to provide an update on the mechanisms underlying the anticancer activity of butein, with a special focus on its effects on different cellular signaling cascades.
Decreased macrophage phagocytic function due to xenobiotic exposures in vitro, difference in sensitivity between various macrophage models Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-16 Hanne Friis Berntsen, Anette Kocbach Bølling, Cesilie Granum Bjørklund, Karin Zimmer, Erik Ropstad, Shanbeh Zienolddiny, Rune Becher, Jørn A. Holme, Hubert Dirven, Unni Cecilie Nygaard, Johanna Bodin
Both autoimmune disease prevalence and exposure to immunotoxic chemicals have increased the last decades. As a first screening of immunotoxic chemicals possibly affecting development of autoimmunity through attenuated macrophage function, we demonstrate a promising model measuring macrophage function in isolated peritoneal macrophages (PCM) from Wistar rats and C57Bl/6 mice. Immunotoxic effects of bisphenol A (BPA) and a selection of perfluoroalkyl acids (PFAAs) were analysed in vitro assessing phagocytic function of macrophages from different sources. Phagocytosis was reduced in PCM of C57Bl/6 mice and Wistar rats after BPA and perfluoroundecanoic acid (PFUnDA) exposure, but not in macrophages derived from human and rat monocyte derived macrophages (MDM). On the other hand, in vitro exposure to mixtures of persistent organic pollutants (POPs) showed similar reductions in rat PCM and rat and human MDM phagocytosis. Reduced phagocytosis was partly due to cytotoxicity. PCM isolated from non-obese diabetic (NOD) mice, interleukin 1α/β knockout (IL-1KO) mice and new-born rats were less sensitive to the xenobiotics than PCM from adult wild type rodents. Finally, in vivo studies with NOD mice verified that POP exposure also decreased the number of pancreatic macrophages in pancreatic islets, reflecting early signs of autoimmunity development, similarly as previously described for BPA.
Evaluation of toxicological endpoints in female zebrafish after bisphenol A exposure Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-16 Ana M. Molina, Nieves Abril, Noelia Morales-Prieto, José G. Monterde, Antonio J. Lora, Nahúm Ayala, Rosario Moyano
Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-16 B. Remington, H.C.H. Broekman, W.M. Blom, A. Capt, R.W.R. Crevel, I. Dimitrov, C.K. Faeste, R. Fernandez-Canton, S. Giavi, G.F. Houben, K.C. Glenn, C.B. Madsen, A.K. Kruizinga, A. Constable
The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or clinical reactions through cross-reactivity. In this paper we review the potential of current methodologies (in silico, in vitro degradation, in vitro IgE binding, animal models and clinical studies) to address these outcomes for risk assessment purposes for new proteins, and especially to identify and characterise the risk of sensitization for IgE mediated allergy from oral exposure. Existing tools and tests are capable of assessing potential crossreactivity. However, there are few possibilities to assess the hazard due to de novo sensitization. The only methods available are in vivo models, but many limitations exist to use them for assessing risk. We conclude that there is a need to understand which criteria adequately define allergenicity for risk assessment purposes, and from these criteria develop a more suitable battery of tests to distinguish between proteins of high and low allergenicity, which can then be applied to assess new proteins with unknown risks.
Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-16 Kit Ieng Kuok, Phoebe Choi In Ng, Xia Ji, Chunming Wang, Wing Wai Yew, Denise P.C. Chan, Jun Zheng, Simon M.Y. Lee, Ruibing Wang
Bedaquiline (BDQ) is a newly approved anti-tuberculosis drug in treating multidrug-resistant tuberculosis. However, it has very poor aqueous solubility and several case reports have proposed that BDQ has potential risk of cardiotoxicity to patients. In this present study, we have explored into employing host-guest interactions between a synthetic receptor, cucurbituril (CB), and BDQ aiming to improve the solubility and reduce the inherent cardiotoxicity of BDQ. HPLC-UV test on the solubility of BDQ in the absence and in the presence of increasing concentrations of CB suggested a host-dependent guest-solubility enhancements. Cardiovascular studies using an in vivo zebrafish model demonstrated that the cardiotoxicity of BDQ was indeed alleviated upon its complexations by the synthetic receptor. Furthermore, our in vitro antibacterial studies suggested that CB formulated BDQ preserved its antimycobacterial efficacy against Mycobacterium smegmatis. Therefore, CB may become a suitable pharmaceutical excipient in formulating BDQ for improving its physiochemical properties (such as solubility), and for alleviating its side effects (such as cardiotoxicity), while the antimycobacterial efficacy of BDQ may be well maintained.
Alleviating the hepatotoxicity of trazodone via supramolecular encapsulation Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-14 Qiaoxian Huang, Shengke Li, Hang Yin, Chunming Wang, Simon M.Y. Lee, Ruibing Wang
In order to develop a novel strategy to alleviate the inherent hepatotoxicity of antidepressant trazodone (TZ), Cucurbituril (CB) was adopted as pharmaceutical excipients and was studied for its capability to reduce the hepatotoxicity of TZ via supramolecular encapsulation. CB was found to form strong 1:1 host-guest complexes with TZ and its metabolite m-chlorophenyl piperazine (mCPP), with binding constants of 1.50 (±0.13) × 106 M−1 and 6.90 (±0.49) × 105 M−1, respectively. The supramolecular complexations were examined by 1H NMR and UV-visible spectroscopic titrations, ESI-MS and ITC. In the presence of 0.5 mM CB, the IC50 values of TZ and mCPP on a human normal liver cell line L02 were increased from 215.5 ± 3.3 μM to 544.1 ± 51.2 μM, and from 166.8 ± 3.8 μM to 241.7 ± 6.8 μM, respectively. Evaluation on a zebrafish model demonstrated that CB (0.1 mM) significantly alleviated the TZ induced liver toxicity, as shown by the level of liver degeneration, liver size and yolk sac retention. Our study may provide a supramolecular strategy to alleviate the hepatotoxicity induced by TZ and its metabolite mCPP, and this strategy may be extendable to other drugs that have inherent hepatotoxicity or other adverse effects.
Survey on the effects of electron beam irradiation on chemical quality and sensory properties on quail meat Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-14 Zahra Derakhshan, Gea Oliveri Conti, Ali Heydari, Motahreh Sadat Hosseini, Fateme Akrami Mohajeri, Hamidreza Gheisari, Samane Kargar, Elham Karimi, Margherita Ferrantee
Introduction Irradiation is one of the intervention strategies for effective control of food-borne pathogen microorganisms, which reduces microbial load and extends the meat shelf life. Materials and Methods This experimental study was carried out on quail meat. Quail meat samples were treated with electron beam irradiation at doses of 0.5, 1, and 3 kGy and stored at 4 ± 1 °C for 15 days. Five days after irradiation, the chemical and organoleptic changes in the quail meat were evaluated for 15 days. Total volatile basic nitrogen and TBA were also measured to investigate chemical changes. Results Irradiation significantly reduced the amount of total volatile basic nitrogen in irradiated samples. Furthermore, the increase of TBA level was significant in irradiated samples, which had a direct correlation with irradiation dose and storage/shelf life duration. Despite the increase of thiobarbituric acid, irradiation had no significant effect on the sensory properties of quail meat. Conclusion Irradiation of quilt meat resulted in extension of the meat shelf life to at least two weeks at refrigeration temperature by decreasing the corrosion-causing microorganisms and improving microbial quality, while the sensory properties of meat were preserved. Regarding the increase in the oxidation level at high doses of the electron beam and the absence of significant differences in the studied dosages in reducing the total amount of total volatile basic nitrogen, it is recommended to apply electron beam irradiation at doses of 1.5 and 3 kGy to extend the meat shelf life and preserve the quality/health of the quail meat.
Chrysin attenuates testosterone-induced benign prostate hyperplasia in rats Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-14 Sherif M. Shoieb, Ahmed Esmat, Amani E. Khalifa, Ashraf B. Abdel-Naim
Benign prostate hyperplasia (BPH) is a common age-related health problem affecting almost 3 out of 4 men in their sixties. Chrysin is a dietary phytoestrogen found naturally in bee propolis and various plant extracts. It possesses antioxidant, anti-inflammatory and anti-proliferative properties. The current study was conducted to explore the role chrysin plays in protection against testosterone-induced BPH in rats. On grounds of a preliminary experiment, a dose of chrysin (50 mg/kg) was chosen for further investigation. Testosterone significantly depleted glutathione, suppressed superoxide dismutase and catalase activities, and elevated lipid peroxidation. Moreover, it markedly scaled down the level of cleaved caspase-3 enzyme, reduced Bax/Bcl-2 ratio and mRNA expression of p53 and p21; conversely, protein expression of proliferating cell nuclear antigen was enhanced. Chrysin alleviated testosterone-induced oxidative stress and restored cleaved caspase-3 level, Bax/Bcl-2 ratio and mRNA expression of p53 and p21 to almost control levels. Chrysin prevented the increase in binding activity of nuclear factor kappa B (NF-κB) p65 subunit, mRNA expression of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 1 receptor (IGF-1R). These data highlight the protective role of chrysin against experimentally-induced BPH. This is attributed - at least partly - to its antioxidant, antiproliferative and proapoptotic properties.
Apigenin promotes TRAIL-mediated apoptosis regardless of ROS generation Food Chem. Toxicol. (IF 3.778) Pub Date : 2017-12-13 Chang-Hee Kang, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi, Cheol Park, Dong-Oh Moon, Gi-Young Kim
Apigenin is a bioactive flavone in several herbs including parsley, thyme, and peppermint. Apigenin possesses anti-cancer and anti-inflammatory properties; however, whether apigenin enhances TRAIL-mediated apoptosis in cancer cells is unknown. In the current study, we found that apigenin enhanced TRAIL-induced apoptosis by promoting caspase activation and death receptor 5 (DR5) expression and a chimeric antibody against DR5 completely blocked the apoptosis. Apigenin also upregulated reactive oxygen species (ROS) generation; however, intriguingly, ROS inhibitors, glutathione (GSH) or N-acetyl-L-cysteine (NAC), moderately increased apigenin/TRAIL-induced apoptosis. Additional results showed that an autophagy inducer, rapamycin, enhanced apigenin/TRAIL-mediated apoptosis by a slight increase of ROS generation. Accordingly, NAC and GSH rather decreased apigenin-induced autophagy formation, suggesting that apigenin-induced ROS generation increased autophagy formation. However, autophagy inhibitors, bafilomycin (BAF) and 3-methyladenine (3-MA), showed different result in apigenin/TRAIL-mediated apoptosis without ROS generation. 3-MA upregulated the apoptosis but remained ROS levels; however, no changes on apoptosis and ROS generation were observed by BAF treatment. Taken together, these findings reveal that apigenin enhances TRAIL-induced apoptosis by activating apoptotic caspases by upregulating DR5 expression regardless of ROS generation, which may be a promising strategy for an adjuvant of TRAIL.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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