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  • 更新日期:2018-10-18
  • Metabolism and disposition of arsenic species from oral dosing with sodium arsenite in neonatal CD-1 mice. III. Toxicokinetics following gavage administration and lactational transfer
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-17
    Nathan C. Twaddle, Michelle Vanlandingham, Frederick A. Beland, Jeffrey W. Fisher, Daniel R. Doerge

    Arsenic is a ubiquitous contaminant, with typical human dietary intake below 1 μg/kg bw/d and extreme drinking water exposures up to ∼50 μg/kg bw/d. The formation and binding of trivalent metabolites are central to arsenic toxicity and strong human evidence suggests special concern for early life exposures in the etiology of adult diseases, especially cancer. This study measured the metabolism and disposition of arsenite in neonatal mice to understand the role of maturation in metabolic activation and detoxification of arsenic. Many age-related differences were observed after gavage administration of arsenite, with consistent evidence in blood and tissues for higher exposures to trivalent arsenic species in neonatal mice related to the immaturity of metabolic and/or excretory functions. The evidence for greater tissue binding of arsenic species in young mice is consistent with enhanced susceptibility to toxicity based on metabolic and toxicokinetic differences alone. Lactational transfer from arsenite-dosed dams to suckling mice was minimal, based on no dosing-related changes in the levels of arsenic species in pup blood or milk collected from the dams. Animal models evaluating whole-life exposure to inorganic arsenic must use direct dosing in early neonatal life to predict accurately potential toxicity from early life exposures in children.

    更新日期:2018-10-18
  • Common risks of adulterated and mislabeled herbal preparations
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-16
    Tjaša Ekar, Samo Kreft

    Due to the growing trend of returning to nature and the fear of adverse reactions from conventional medicines, people are increasingly resorting to the use of herbal preparations. Because of long-term use and natural origin these preparations give a sense of security. But herbal formulations also possess undesirable effects and, among other dangers, present a risk connected with deliberate addition of synthetic compounds, deliberate or unintentional replacement of the plant species or simply a risk of mislabeling. While the replacement of the plant species occurs in a very different groups of herbal products, reports of added illicit synthetic substances often include groups of herbal weight-loss preparations, sexual enhancers, preparations for treatment of rheumatic and inflammatory diseases, antidiabetic and blood pressure lowering preparations. In the world of Internet ordering, these are the dangers that everyone should be aware of. In this article, we reviewed the safety issues related to adulterated or mislabeled herbal products.

    更新日期:2018-10-17
  • Pre-validation study of alternative developmental toxicity test using mouse embryonic stem cell-derived embryoid bodies
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-16
    Jae-Hwan Lee, Seon Young Park, Changhwan Ahn, Cho-Won Kim, Ji-eun Kim, Na Rae Jo, Hee Young Kang, Yeong-Min Yoo, Eui-Man Jung, Eun Mi Kim, Ki-Suk Kim, Kyung-Chul Choi, Sung Duck Lee, Eui-Bae Jeung

    The embryoid body test (EBT) is a developmental toxicity test method that assesses the half inhibitory concentrations of substances in the area of embryoid bodies (EBs), and in the viability of mouse embryonic stem cells (ESCs) and fibroblasts (3T3 cells) following chemical exposure for three and four days, respectively. In the previous study, the EBT showed more advanced than the embryonic stem cell test (EST) from the European Centre for the Validation of Alternative Methods (ECVAM) applying cardiac differentiation of mouse ESCs, because the EBT greatly reduced the exposure time, labor, and amount of materials required, and misclassification of embryotoxic potential. This pre-validation study evaluated the predictive accuracy of the EBT using 26 coded test substances by two steps: intra-laboratory and inter-laboratory reproducibility tests. Since some substances have different embryotoxic potentials at different pregnancy periods, in this study, a new prediction model consisting of non-toxic and toxic classes was used, instead of the existing prediction model assessing embryotoxicants in four classes. The results of the intra- and inter-laboratory tests were highly accurate (above 80%) when substances were classified using the predictive model. In conclusion, EBT can accurately classify various embryotoxicants in a short time with less effort and greater validation.

    更新日期:2018-10-17
  • Role of neurotransmitters 5-hydroxytryptamine and substance P in anorexia induction following oral exposure to the trichothecene T-2 toxin
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-16
    Kun Sheng, Xi Lu, Jianming Yue, Wei Gu, Chao Gu, Haibin Zhang, Wenda Wu

    Trichothecene mycotoxins, a family of common contaminants on cereal grains, are known to negatively impact human and animal health with adverse effect on food consumption being of particular concern. T-2 toxin has been previously demonstrated to induce anorectic response in several animal species including mouse, rat, rabbit. Although the T-2 toxin-induced anorectic response has been associated with the release of gut satiety hormone, much less is known about the role of neurotransmitter in this response. To address this gap, we employed a nocturnal mouse food refusal model to test the hypothesis that neurotransmitters 5-hydroxytryptamine (5-HT) and substance P (SP) mediate anorexia induction by T-2 toxin. Elevations of plasma 5-HT and SP markedly corresponded to anorexia induction following oral exposure to T-2 toxin. Direct administration of exogenous 5-HT and SP induced anorectic responses similar to T-2 toxin. The 5-HT3 receptor (5-HT3R) antagonist granisetron evoked a dose-dependent attenuation of both 5-HT- and T-2 toxin-induced anorectic responses. Pretreatment with neurokinin-1 receptor (NK-1R) antagonist Emend® dose-dependently attenuated both SP- and T-2 toxin-induced anorectic responses. To summarize, the results suggest that both 5-HT and SP play important roles in anorexia induction by T-2 toxin. 5-HT is more potent and long-acting than SP in this response.

    更新日期:2018-10-16
  • Ginsenosides, catechins, quercetin and gut microbiota: Current evidence of challenging interactions
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-16
    Rosaria Santangelo, Andrea Silvestrini, Cesare Mancuso

    Recent studies have shown the role of gut microbiota in favoring the absorption of herbal products and the transformation of their active principles into metabolites endowed with biological activity. This review focuses on the evidence supporting the changes occurring, after metabolic reactions by specific bacteria that colonize the human gut, to ginseng-derived ginsenosides, green tea-derived catechins, and quercetin, this latter being a flavonoid aglycon bound to sugars and abundant in some vegetables and roots. Furthermore, the results of several preclinical and clinical studies demonstrating the potential beneficial effects of the active metabolites generated by these biotransformations on ginsenosides, catechins and quercetin will be reported.

    更新日期:2018-10-16
  • Genotoxicity of heterocyclic amines (HCAs) on freshly isolated human peripheral blood mononuclear cells (PBMC) and prevention by phenolic extracts derived from olive, olive oil and olive leaves
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-12
    Raffaela Fuccelli, Patrizia Rosignoli, Maurizio Servili, Gianluca Veneziani, Agnese Taticchi, Roberto Fabiani

    In this study we investigated the genotoxic potential of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, (PhIP); 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline, (IQ); 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline, (MeIQx) and 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (DiMeIQx) on human freshly isolated peripheral blood mononuclear cells (PBMCs) by the comet assay. The preventive ability of three different phenolic extracts derived from olive (O-PE), virgin olive oil (OO-PE) and olive leaf (OL-PE) on PhIP induced DNA damage was also investigated.PhIP and IQ induced a significant DNA damage at the lowest concentration tested (100 μM), while the genotoxic effect of MeIQx and DiMeIQx become apparent only in the presence of DNA repair inhibitors Cytosine b-D-arabinofuranoside and Hydroxyurea (AraC/HU). The inclusion of metabolic activation (S9-mix) in the culture medium increased the genotoxicity of all HCAs tested. All three phenolic extracts showed an evident DNA damage preventive activity in a very low concentration range (0.1–1.0 μM of phenols) which could be easily reached in human tissues “in vivo” under a regular intake of virgin olive oil. These data further support the observation that consumption of olive and virgin olive oil may prevent the initiation step of carcinogenesis. The leaf waste could be an economic and simple source of phenolic compounds to be used as food additives or supplements.

    更新日期:2018-10-14
  • Dietary furocoumarins and skin cancer: A review of current biological evidence
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-11
    Melissa M. Melough, Ock K. Chun

    Furocoumarins are a class of compounds produced by several plant species, including some popularly consumed by humans. Furocoumarins are known to be well absorbed from food sources, and can be rapidly distributed into several tissues including the skin. In human skin, when exposed to UV radiation, furocoumarins may become photoactivated and form interstrand crosslinks with DNA, thereby disrupting DNA transcription. Because of this property, furocoumarins have been combined as topical or oral agents with UV irradiation as a phototherapy to treat multiple skin conditions, yet these treatments have been shown to increase risk of both melanoma and non-melanoma skin cancer. Whether or not dietary furocoumarin exposure may confer the same risk is not yet known. This review summarizes the current evidence regarding the activities of ingested furocoumarins, with particular focus on how dietary furocoumarins are absorbed, metabolized, and distributed throughout the body, and their interactions with various cellular components that may underlie a potential relationship with skin cancer.

    更新日期:2018-10-12
  • In vivo evaluation of effect of anthocyanin-rich wheat on rat liver microsomal drug-metabolizing cytochromes P450 and on biochemical and antioxidant parameters in rats
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-11
    Prokop Jiří, Anzenbacher Pavel, Mrkvicová Eva, Pavlata Leoš, Zapletalová Iveta, Šťastník Ondřej, Martinek Petr, Kosina Pavel, Anzenbacherová Eva
    更新日期:2018-10-12
  • 2,6-Dimethoxy-1,4-benzoquinone, isolation and identification of anti-carcinogenic, anti-mutagenic and anti-inflammatory component from the juice of Vitis coignetiae
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-11
    Tomonori Kamiya, Yusuke Tanimoto, Nana Fujii, Tomoe Negishi, Toshinori Suzuki, Tsutomu Hatano, Sakae Arimoto-Kobayashi

    Previously we demonstrated the anti-tumorigenic, anti-mutagenic and anti-inflammatory effects of the juice of Vitis coignetiae (yamabudo), and identified caftaric acid as an anti-mutagenic component from the juice. In the present study, we investigated the isolation of anti-inflammatory components in yamabudo juice supposing that the anti-inflammatory components in yamabudo are also responsible for the anti-tumorigenic activity. The suppressing effect on nitric oxide production in mouse leukemic monocyte with LPS was used as a separation marker. Three components comprising 2,6-dimethoxy-1,4-benzoquinone (DBQ), fertaric acid and caftaric acid were isolated and identified from the juice of V. coignetiae as anti-inflammatory ingredients. Inhibitory effects were found of DBQ on the mutagenicity of dimethylbenzo[a]anthracene, aflatoxin B1, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the Ames test. Topical application of DBA significantly inhibited TPA-induced edema of mouse ears. The anti-tumorigenic effect of DBQ on the promotion and initiation stages of mouse skin tumorigenesis was investigated, and topical administration of DBQ on the promotion stage significantly decreased tumor development in mice skin. DBQ is a potential candidate for the chemopreventive effect of V. coignetiae.

    更新日期:2018-10-12
  • Metabolism of 4-methylimidazole in fischer 344 rats and B6C3F1 mice
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-11
    Timothy R. Fennell, Scott L. Watson, Suraj Dhungana, Rodney W. Snyder

    4-Methylimidazole (4-MeI) is a widely used chemical, also identified as a by-product of heating foods. In cancer bioassays, 4-MeI induced lung tumors in mice, but not in rats. To establish if metabolic differences could explain species difference in carcinogenicity, this study investigated metabolism of 4-MeI in rat and mouse lung and liver microsomes and S-9 fractions, and in vivo in rats and mice. No metabolites were detected in rat or mouse lung and liver microsomes, or lung S-9 fractions. Male and female F-344 rats and B6C3F1 mice were administered 50 and 150 mg/kg [14C] 4-MeI by gavage. Excreta, exhaled CO2 and volatiles were collected for 48 h. Elimination was mainly via urine, with 79–89% of the radioactivity in urine in rats and 41–70% in mice. Most of the radioactivity (71–88%) in urine was unchanged 4-MeI. Additional radioactive peaks (the largest metabolite was 8–18%) were characterized by LC-MS/MS as 4-hydroxymethylimidazole, its glucuronide, and other oxidized products, including methylhydantoin. 4-MeI was largely excreted unchanged in rats and mice with limited oxidative metabolism and conjugation. 4-MeI was not oxidized in subcellular fractions from rat and mouse lung and liver. Overall, the metabolism of 4-MeI appeared similar between rats and mice.

    更新日期:2018-10-12
  • Tea polyphenols direct Bmal1-driven ameliorating of the redox imbalance and mitochondrial dysfunction in hepatocytes
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-11
    Guoyuan Qi, Wanqiang Wu, Yashi Mi, Renjie Shi, Keyu Sun, Runnan Li, Xiao Liu, Xuebo Liu
    更新日期:2018-10-12
  • 1,3-Dichloro-2-Propanol inhibits autophagy via P53/AMPK/mTOR pathway in HepG2 cells
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-11
    Bijun Cheng, Jing Lu, Tianjiao Li, Zhuoqun Meng, Meitong Liu, Maocheng Sun, Shuang Guan
    更新日期:2018-10-11
  • Bisphenol A exhibits cytotoxic or genotoxic potential via oxidative stress-associated mitochondrial apoptotic pathway in murine macrophages
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-09
    Fu-Mei Huang, Yu-Chao Chang, Shiuan-Shinn Lee, Yung-Chyuan Ho, Ming-Ling Yang, Hui-Wen Lin, Yu-Hsiang Kuan
    更新日期:2018-10-10
  • Development and validation of a ready to use cryo-EROD assay for the standardized screening of dioxins and dioxin-like compounds in foodstuffs
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-06
    Walkiria Levy, Karl-Werner Schramm, Florian Mertes, Bernhard Henkelmann, Martina Maywald, Peter Uciechowski, Alexander Loa, Johannes Haedrich, Ines Thiem, Henner Hollert, Roland Goerlich, Thorsten Bernsmann, Lothar Rink

    Recent European regulations have indicated the need for new bioanalytical screening methods capable of monitoring dioxin and dioxin-like compounds in foodstuffs and environmental samples, cost-effectively and with a quicker turnaround. Cryo-cells of the hepatic H4IIE line preserved in 96-well plates were exposed to sample extracts prepared from various foodstuffs and analysed for their content of dioxins and dioxin-like compounds by means of the 7-Ethoxyresorufin-O-Deethylase (EROD)-assay in two laboratories. Assay data were compared between both laboratories and results from instrumental analysis used as a confirmatory method. Additionally, cut-off values for the different studied matrices were derived. The current European regulation regarding methods of analysis for the control of foodstuffs was applied with the aim of determining the feasibility of the cryo-methodology. Results obtained in both laboratories were in congruence with the required validation parameters of the Commission Regulation (EU) No 2017/644. Cut-off values should be established matrix-dependent to reduce the rate of false compliant results and to keep the rate of false non-compliant results under control. In summary, the ready-to-use cryo-assay method for the bioanalytical screening of foodstuffs in control laboratories without cell-culture facilities has successfully proven to be accurate, far quicker and more cost effective than current methods.

    更新日期:2018-10-06
  • Maternal BDE-209 exposure during lactation perturbs steroidogenesis, germ cell kinetics and THRα1 expression in testes of prepubertal mice offspring
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-06
    Debarshi Sarkar, Vinay Kumar Singh, Shio Kumar Singh

    Decabromodiphenyl ether (BDE-209), a congener of Polybrominated diphenyl ethers (PBDEs), is used as flame retardant and affects thyroid homeostasis. Thyroid hormones (THs) play crucial role in Leydig cell differentiation and steroidogenesis during early life. Present study examined the effect of maternal BDE-209 exposure during lactation on testicular steroidogenesis and spermatogenesis in relation to thyroid hormone receptor alpha 1 (THRα1) and possible mechanism(s) of its action in prepubertal Parkes mice offspring. Lactating female Parkes mice were orally gavaged with 500, and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28. Lactating mothers and male pups were sacrificed on PND 28. Maternal BDE-209 exposure markedly affected testicular histopathology, steroidogenesis and germ cell dynamics with downregulated expressions of various steroidogenic markers in mice offspring. Serum THs levels were markedly reduced in both pups and lactating mothers compared to controls. Expression of proliferating cell nuclear antigen and THRα1 also deceased in testes of BDE-209-exposed mice offspring. In silico analysis by molecular docking was performed successfully for steroidogenic facor-1 (SF-1) and THRα1 with BDE-209 and T3. Maternal BDE-209 exposure during lactation affects testicular steroidogenesis, spermatogenesis and expression of THRα1 in prepubertal mice offspring through downregulation of SF-1.

    更新日期:2018-10-06
  • Role of AMPK pathway in lead-induced endoplasmic reticulum stress in kidney and in paeonol-induced protection in mice
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-06
    Chan-Min Liu, Hui-Xin Yang, Jie-Qiong Ma, Wei Yang, Zhao-Jun Feng, Jian-Mei Sun, Chao Cheng, Jun Li, Hong Jiang
    更新日期:2018-10-06
  • Complementary feeding may pose a risk of simultaneous exposures to aflatoxin M1 and deoxynivalenol in Indian infants and toddlers: Lessons from a mini-survey of food samples obtained from Kolkata, India
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-06
    Phani M. Gummadidala, Mayomi H. Omebeyinje, James A. Burch, Paramita Chakraborty, Prasanta K. Biswas, Koyeli Banerjee, Qian Wang, Rubaiya Jesmin, Chandrani Mitra, Peter D.R. Moeller, Geoffrey I. Scott, Anindya Chanda
    更新日期:2018-10-06
  • Hypocholesterolaemic and antioxidant properties of Olea europaea L. leaves from Chlef province, Algeria using in vitro, in vivo and in silico approaches
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-04
    M. Cheurfa, H.H. Abdallah, R. Allem, A. Noui, C.M.N. Picot-Allain, F. Mahomoodally

    Aqueous and ethanol extracts prepared from leaves of Olea europaea L. were evaluated for in vitro antioxidant and in vivo hypocholesterolemic effect. The result of administration of O. europaea leaf extracts on serum total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in hypercholesterolaemic mice was evaluated. In addition, rutin and luteolin, reported to occur naturally in O. europaea leaves, were docked against HMG-CoA reductase, the rate-limiting enzyme in cholesterol metabolism. Mice treated with both extracts showed reduced total cholesterol (246.6 and 163.4 mg/dl, for mice groups treated with respective extracts) and LDL (150.16 and 81.28 mg/dl, for mice groups treated with respective extracts) levels as compared to the hypercholesterolaemic group (total cholesterol 253.00 mg/dl and LDL 160.00 mg/dl). Mice treated with aqueous extract (200 mg/kg body weight) showed significantly reduced triglyceride and VLDL levels as compared to the group treated with atorvastatine. HDL level of mice administered with O. europaea aqueous extract was comparable to the atorvastatine-treated group. The ethanol extract of O. europeae leaves was a potent antioxidant (IC50 69.15 mg/ml, % inhibition 54.98, 82.63 mg ascorbic acid equivalent/g extract, 7.53 mol of Fe2+/g extract, and % inhibition 49.71, for the DPPH, β-carotene bleaching, total antioxidant capacity, FRAP, and ferric thiocyanate assays, respectively). Docking studies revealed that rutin showed higher binding affinity with HMG-CoA reductase as compared to luteolin. Data gathered from this study support the development of a prophylactic biomedicine from O. europaea leaves for the management of hypercholesterolemia and atherosclerosis.

    更新日期:2018-10-04
  • Toxicogenomic responses to zearalenone in Caenorhabditis elegans reveal possible molecular mechanisms of reproductive toxicity
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-04
    Zhendong Yang, Kathy S. Xue, Xiulan Sun, Phillip L. Williams, Jia-Sheng Wang, Lili Tang

    In this study, the possible molecular mechanisms of zearalenone (ZEA)-induced reproductive and developmental toxic effects in Caenorhabditis elegans (C. elegans) were investigated. Differential gene expression profiles were identified, and 171, 245, and 3149 genes were down- or up-regulated (>2.0 fold) in 10, 20, and 40 μg/ml ZEA treated groups, respectively, as compared to untreated controls. Pathway specific mapping showed that the major differentially expressed genes were collagen synthetic pathways regulating genes, col-121 and dpy-17. Real-time PCR reconfirmation of key genes, related to cuticle collagen synthetic pathway, found dramatic changes in the expression of the genes dpy-31, sqt-3, col-121, and dpy-17 following exposure to ZEA (40 μg/ml), which indicated the significance of these genes in ZEA-induced toxicity. Cuticle collagen plays many key roles in the development and reproduction of C. elegans. The hypersensitive responses in transgenic and mutant worms also confirmed the roles of these genes in lethality and reproductive response to ZEA exposure, which indicates that ZEA blocked the normal collagen processing and cuticle formation. Taken together, our results demonstrate that disruption of the collagen biosynthetic pathway might be a key mechanism in ZEA-induced reproductive and developmental toxic effects in C. elegans.

    更新日期:2018-10-04
  • Renal toxicity through AhR, PXR, and Nrf2 signaling pathway activation of ochratoxin A-induced oxidative stress in kidney cells
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-03
    Hyun Jung Lee, Min Cheol Pyo, Hye Soo Shin, Dojin Ryu, Kwang-Won Lee
    更新日期:2018-10-04
  • Phytochemical analysis and anti-inflammatory effects of Filipendula vulgaris moench extracts
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-03
    Jelena Katanić, Eva-Maria Pferschy-Wenzig, Vladimir Mihailović, Tatjana Boroja, San-Po Pan, Stefanie Nikles, Nadine Kretschmer, Gvozden Rosić, Dragica Selaković, Jovana Joksimović, Rudolf Bauer
    更新日期:2018-10-04
  • Coffee, caffeine, chlorogenic acid, and the purinergic system
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-03
    Naiara Stefanello, Roselia Spanevello, Sabina Passamonti, Lisiane Porciúncula, Carla Denise Bonan, Ayodeji Augustine Olabiyi, João Batista Teixeira da Rocha, Charles Elias Assmann, Vera Maria Morsch, Maria Rosa Chitolina Schetinger
    更新日期:2018-10-04
  • Ochratoxin A induces cytoprotective autophagy via blocking AKT/mTOR signaling pathway in PK-15 cells
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-01
    Gang Qian, Dandan Liu, Lili Hou, Mohammed Hamid, Xingxiang Chen, Fang Gan, Kehe Huang

    Ochratoxin A (OTA) could cause a variety of toxicological effects especially nephrotoxicity in animals and humans. Autophagy is a highly conserved metabolic process that plays an important role in the maintenance of cellular homeostasis under stress. However, the role of autophagy in OTA-induced nephrotoxicity is unknown. In the present study, we demonstrated that OTA treatment at 2.0–8.0 μM could increase cytotoxicity of PK-15 cells by inducing apoptosis as shown by the increased Annexin V/PI staining, increased caspase-3 and PARP cleavage and increased apoptotic nuclei. Meantime, autophagy was triggered when OTA was administrated, as indicated by markedly increased expressions of LC3-II, ATG5 and Beclin-1, accumulation of GFP-LC3 dots and increased double- or single-membrane vesicles. OTA treatment decreased p-AKT and p-mTOR activities, and OTA-induced autophagy was inhibited when insulin was applied. Furthermore, OTA treatments with autophagy inhibitors (3-methyladenine or chloroquine) or knockdown of autophagy-related genes (ATG5 or Beclin-1) resulted in significantly reduced autophagy level and enhanced cytotoxicity. In conclusion, OTA induces cytoprotective autophagy against its cytotoxicity and inactivation of AKT/mTOR axis plays a critical role in autophagy induction.

    更新日期:2018-10-02
  • Natural activators of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and their pharmacological activities
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-10-02
    Mahdi Vazirian, Seyed Mohammad Nabavi, Samineh Jafari, Azadeh Manayi

    Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme which monitors cellular energy status and regulates metabolism with energy balance. AMPK activation, as a master regulator of metabolism, plays role in key tissues like liver, skeletal muscles, and heart as well as central nervous system (CNS). Activation of the enzyme by indirect activators attracts scientific attentions to treat diabetes, obesity, cancer, and other related metabolic disorders like physiological and pathophysiological states in CNS. A number of hormones and pharmacological agents have been reported to activate AMPK including paroxetine, metformin, thiazolidinediones, adiponectin, leptin, interleukin-6, and etc. AMPK activity is prominent in regulation of glucose, lipid, and proteins metabolism as well as mitochondrial biogenesis and autophagy. Activation of AMPK in the liver decrease blood glucose and in skeletal muscles stimulates glucose uptake independently of insulin through modulation of activity of several downstream substrates. Activation of AMPK inhibits synthesis and induces oxidation of fatty acids, which may reduce ectopic lipid accumulation and improve insulin action. The enzyme activation promotes cardiovascular homeostasis by ensuring optimum redox balance of heart and vascular tissue. In addition, AMPK signaling may link to cancer development via regulation of checkpoints of cell cycle. Numerous of conventional drugs have been derived from natural resources, while the application of this fruitful source of chemical structures have not been explored in depth. A number of these compounds are discussed in this review that exhibit beneficial effects in metabolic disorders through AMPK activation.

    更新日期:2018-10-02
  • Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-30
    Charles M. Skinner, Isabelle R. Miousse, Laura E. Ewing, Vijayalakshmi Sridharan, Maohua Cao, Haixia Lin, D. Keith Williams, Bharathi Avula, Saqlain Haider, Amar G. Chittiboyina, Ikhlas A. Khan, Mahmoud A. ElSohly, Marjan Boerma, Bill J. Gurley, Igor Koturbash

    Herbal dietary supplement (HDS)-induced hepato- and cardiotoxicity is an emerging clinical problem. In this study, we investigated the liver and heart toxicity of HDS OxyELITE-PRO™ New Formula (OEP-NF), a dietary supplement marketed for weight loss and performance enhancement that was recently withdrawn from the market. Using a novel NZO/HlLtJ obese mouse model, we demonstrated that administration of clinically relevant mouse equivalent doses (MED) of OEP-NF produced cardio- and hepatotoxic risks following both short- and long-term administration schedules. Specifically, gavaging female NZO/HlLtJ with up to 2X MED of OEP-NF resulted in 40% mortality within two weeks. Feeding mice with either 1X or 3X MED of OEP-NF for eight weeks, while not exhibiting significant effects on body weights, significantly altered hepatic gene expression, increased the number of apoptotic and mast cells in the heart and affected cardiac function. The degree of toxicity in NZO/HlLtJ mice was higher than that observed previously in non-obese CD-1 and B6C3F1 strains, suggesting that an overweight/obese condition can sensitize mice to OEP-NF. Adverse health effects linked to OEP-NF, together with a number of other hepato- and cardiotoxicity cases associated with HDS ingestion, argue strongly for introduction of quality standards and pre-marketing safety assessments for multi-ingredient HDS.

    更新日期:2018-10-01
  • Review on rosmarinic acid extraction, fractionation and its anti-diabetic potential
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-28
    Yi Lei Ngo, Cher Haan Lau, Lee Suan Chua
    更新日期:2018-09-29
  • Postnatal exposure to chlorpyrifos produces long-term effects on spatial memory and the cholinergic system in mice in a sex- and APOE genotype-dependent manner
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-29
    Laia Guardia-Escote, Pia Basaure, Jordi Blanco, Maria Cabré, Cristian Pérez-Fernández, Fernando Sánchez-Santed, José L. Domingo, Maria Teresa Colomina

    Organophosphorus pesticides – and in particular chlorpyrifos (CPF) – are extensively used worldwide. They mainly exert their toxicity by targeting the cholinergic system. Several studies suggested that the gene coding for apolipoprotein E (apoE), which is a risk factor for several diseases, can also confer different vulnerability to toxic insults. This study was aimed at assessing the long-term effects of postnatal exposure to CPF on learning and memory as well as the expression levels of several genes involved in cholinergic neurotransmission in mice. Both male and female apoE4-TR and C57BL/6 mice were exposed to either 0 or 1 mg/kg/day of CPF by oral gavage using a micropipette on postnatal days 10–15. At 9 months, they were tested in a Morris Water Maze (MWM) and the gene expression in the frontal cortex and hippocampus was evaluated. Our results show that, in males, CPF had an effect on the spatial retention, while in females, it altered the expression levels of nicotinic receptors. Furthermore, apoE4-TR mice performed the worst during the MWM retention and presented low expression levels in a considerable number of cholinergic genes. Taken together, the current results reveal long-term effects in mice nine months after postnatal exposure to CPF, which are modulated by sex and apoE4 genotype.

    更新日期:2018-09-29
  • Preliminary assessment of galaxolide bioaccessibility in raw and cooked FISH
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-29
    Laura Trabalón, Ricardo N. Alves, Óscar Castro, Martí Nadal, Francesc Borrull, Eva Pocurull, António Marques

    Generally, dietary intake assessment and risk characterization are evaluated using contaminant concentration in raw fish while it is usually ingested cooked, which can cause an overestimation because one of the essential issues for risk-benefit analysis is to determine the maximum amount of a contaminant that can be released from the food matrix and be absorbed by the human body, called bioaccessibility. Moreover, despite most seafood products are cooked before consumption, risk assessment is still evaluated in raw products, strongly affecting public health guidelines. In the present study, an in vitro bioaccessibility assay was performed for Galaxolide (HHCB) in fish samples. Raw spiked hake samples were in vitro digested and aliquots of each fraction of the digestion process were analysed. HHCB was quantitatively present in the bioaccessibility fraction. The effect of fish cooking on HHCB was also evaluated in cod and mackerel samples. Results demonstrate that steaming and grilling processes lead to a loss of 50–70% HHCB in fish.

    更新日期:2018-09-29
  • Metabolism and disposition of arsenic species from controlled dosing with sodium arsenite in adult female CD-1 mice. III. Toxicokinetic studies following oral and intravenous administration
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-29
    Nathan C. Twaddle, Michelle Vanlandingham, Jeffrey W. Fisher, Daniel R. Doerge

    Arsenic is a ubiquitous contaminant, with typical dietary intake below 1 μg/kg bw/d and drinking water exposures up to 50 μg/kg bw/d. Arsenic exposures are associated with human diseases and doses of toxicological concern are similar to typical dietary intake. Metabolism of arsenite to dimethylarsinate (DMAV) by arsenite-3-methyltransferase (As3MT) promotes clearance, but also generates reactive trivalent intermediates that bind extensively to cellular thiols. This study measured pentavalent and trivalent arsenic species in blood and tissues after oral and intravenous administration of arsenite (50 μg/kg bw). After oral administration, the intestine and liver contained elevated levels of AsIII and MMAIII, relative to erythrocytes, lung, and kidney, suggesting incomplete conversion to DMA during first-pass metabolism. However, blood concentrations of the predominant species, DMA, were similar for oral and intravenous dosing. While all tissues examined contained DMAIII, muscle, brain, and plasma had undetectable levels of MMAIII. Tissue levels of arsenic species were similar following intravenous vs. oral administration, except lower in the intestine. The results confirm the role of metabolism in producing fluxes of putatively toxic trivalent arsenic intermediates. Tissue dosimetry suggests that the intestine, liver, lung, and kidney could be more susceptible to effects of bound arsenic, relative to muscle and brain.

    更新日期:2018-09-29
  • A likely placental barrier against methylmercury in pregnant rats exposed to fish-containing diets
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-29
    Sébastien Cambier, Masatake Fujimura, Jean-Paul Bourdineaud
    更新日期:2018-09-29
  • Antidepressant-like effect of salidroside and curcumin on the immunoreactivity of rats subjected to a chronic mild stress model
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-27
    Liliya V. Vasileva, Kremena E. Saracheva, Mariya V. Ivanovska, Atanaska P. Petrova, Andrey S. Marchev, Milen I. Georgiev, Mariana A. Murdjeva, Damiyanka P. Getova
    更新日期:2018-09-28
  • FDA regulatory approach to steviol glycosides
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-27
    Judith D. Perrier, Jeremy J. Mihalov, Susan J. Carlson

    Stevia rebaudiana (Bertoni) Bertoni, commonly known as stevia, is a plant native to South America that has been cultivated for hundreds of years. In 1995, FDA revised its import alert on stevia leaves and extracts to allow for their use as dietary ingredients in dietary supplements. In 2007, the Joint FAO/WHO Expert Committee on Food Additives established a safe level of intake and specifications for steviol glycosides that included a minimum purity of 95% of seven named steviol glycosides. In 2008, FDA responded without questions to a Generally Recognized as Safe (GRAS) notice for the use of highly purified steviol glycosides obtained from stevia leaves as a general purpose sweetener in food. Due to the existing import alert, FDA filed, evaluated, and has not objected to more than 50 GRAS notices for the use of various high-purity steviol glycosides as sweeteners in food. In this paper, we highlight FDA's practices for filing and evaluating GRAS notices for steviol glycosides. We also provide a summary of the data and information presented in GRAS notices for steviol glycosides in the GRAS Notification program. FDA has received a new wave of GRAS notices that include alternative biotechnological methods for production of steviol glycosides.

    更新日期:2018-09-28
  • Toxicological evaluation of 2-dodecylcyclobutanone, a unique radiolytic compound of palmitic acid
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-27
    Beom-Seok Song, Yona Kim, Yeung Bae Jin, Il-Jun Kang, Kang Sung Kim, Jong-Heum Park, Jae-Kyung Kim, Ha-Young Park, Sang-Hee Jeong

    This study was conducted to evaluate the toxic effects and potency of 2-dodecylcyclobutanone (2-dDCB), a unique compound derived from palmitic acid via irradiation. In a series of assays of bacterial reverse-mutation, in vitro chromosomal aberration, and in vivo micronucleus, negative responses were found by the treatment of 2-dDCB comparing vehicle control, dimethyl sulfoxide or corn oil. In the acute oral toxicity test, all of the mice administrated 2-dDCB survived, and there were no clinical and necropsy signs observed at any doses (0, 300, and 2000 mg/kg body weight) during the experimental period of 14 days. These results suggested that 2-dDCB is a relatively non-toxic substance with median lethality dose higher than 2000 mg/kg body weight. Moreover, there were no adverse effects noted in rats orally administrated 2-dDCB everyday via gavage for 28 days, even at the highest dose (2.0 mg/kg body weight/day) tested, which is 1000-times higher than the human daily intake of 2-dDCB estimated through an extreme exposure scenario. Overall, these results indicate that 2-dDCB is not likely to raise any human health concerns and irradiated foods containing palmitic acid can be recognized as safe for human consumption under the current international regulation systems for food irradiation.

    更新日期:2018-09-27
  • Tanshinone IIA attenuates TNF-α induced PTX3 expression and monocyte adhesion to endothelial cells through the p38/NF-κB pathway
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-27
    Jian Fang, Qiuyan Chen, Baozhu He, Jiaxuan Cai, Yawen Yao, Yi Cai, Suowen Xu, Kannan RR. Rengasamy, Shanmugaraj Gowrishankar, Shunmugiah Karutha Pandian, Tiansheng Cao

    Tanshinone IIA is one of the most predominant bioactive constituents of Danshen, a traditional Chinese medicinal plant with multiple cardiovascular protective actions. Although Tanshinone IIA has been well documented for its endothelial protective efficacy, studies unveiling the mechanism and/or molecular targets for its pharmacological activity are still inadequate. In recent studies, it has been envisaged that the expression of pentraxin 3 (PTX3) was associated with atherosclerotic cardiovascular diseases (ACVD). Therefore, the current study was designed to evaluate the possible role of Tanshinone IIA in influencing the expression of PTX3 in endothelial cells and thereby prevents endothelial dysfunction. Molecular analyses through real-time PCR, western blot, and ELISA revealed that Tanshinone IIA down-regulates PTX3 gene expression as well as protein secretion in human endothelial cells in the presence or absence of TNF-α. Besides, Tanshinone IIA inhibits the adhesion of THP1 cells (a monocytic cell line) to activated-endothelial cells stimulated with TNF-α. Furthermore, mechanistic studies uncovered the role of p38 MAPK/NF-κB pathway in Tanshinone II-A mediated pharmacological effects. Thus, the present study exemplifies the manifestation of Tanshinone IIA as a plausible alternative natural remedy for ACVD by targeting PTX3.

    更新日期:2018-09-27
  • Presence of mycotoxins in ready-to-eat food and subsequent risk assessment
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-25
    D. Carballo, J.C. Moltó, H. Berrada, E. Ferrer

    A study on a set of ready-to-eat meals (n = 328) based on cereals, legumes, vegetables, fish and meat was carried out to determine the natural presence of twenty-seven mycotoxins by both liquid chromatography and gas chromatography coupled mass spectrometry in tandem (MS/MS) after QuEChERS extraction. The occurrence of mycotoxins was headed by cereal samples with 35% of samples contaminated by at least one mycotoxin followed by vegetables (32%), legumes (15%) and lastly, 9% of fish and meat samples were contaminated. DON was the most detected mycotoxin in vegetables, meat, fish and cereals with an incidence of 13% 18% 19% and 60%, respectively, and the highest mean levels were found in fish (1.19 μg/kg) and vegetable (1.53 μg/kg), respectively. The highest levels means were for HT-2 toxin ranging from 4.03 to 7.79 μg/kg, in cereal and legume samples respectively. In this last, HT-2 toxin was also the most prevalent (54%). In meat samples, OTA resulted with highest value with 8.09 μg/kg. Likewise, PCA analysis revealed a high correlation between the mycotoxins and the food groups analyzed. The findings indicate that there is no toxicological concern associated with exposure to mycotoxins for consumers as all levels were in accordance with the legislation.

    更新日期:2018-09-26
  • Dietary effects of Sideritis scardica “mountain tea” on human in vivo activities of xenobiotic metabolizing enzymes in healthy subjects
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-25
    Elias Begas, Thomas Kilindris, Evangelos Kouvaras, Agoritsa Tsioutsioumi, Demetrios Kouretas, Eftihia K. Asprodini

    Sideritis scardica is an endemic plant of the Balkan Peninsula traditionally used as herbal tea for inflammation, and gastric disorders. Aqueous herbal extracts may affect the activity of Phase I and II enzymes involved in xenobiotic metabolism. The purpose of the present study was to determine whether Sideritis scardica decoction alters the activity of CYP1A2, CYP2A6, XO, NAT2 and UGT1A1/1A6 enzymes in humans.Fourteen healthy subjects consumed Sideritis scardica decoction for six days. Enzyme phenotyping was assessed in saliva and urine using caffeine and paracetamol metabolite ratios as follows: CYP1A2: 17X/137Χ (saliva) and (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X), NAT2: AFMU/(AFMU+1U+1X) and UGT1A1/1A6 glucuronidated/total paracetamol (urine).After Sideritis scardica intake, CYP1A2 index was reduced by ∼16% and ∼8% in saliva (before: 0.54 ± 0.18, after: 0.46 ± 0.09; p = 0.08) and urine (before:3.59 ± 0.52, after:3.67 ± 0.78; p = 0.12), respectively. CYP2A6 index was significantly reduced only in males (before: 0.76 ± 0.08, after: 0.67 ± 0.07; p = 0.004) suggesting a sexual dimorphism in CYP2A6 inhibition. There was no effect of Sideritis scardica treatment on XO, NAT2 or UGT1A1/1A6 indices.Usual consumption of the aerial parts of Sideritis scardica decoction is unlikely to result in herb-drug interactions involving the enzymes studied, with the exception of potential herb-CYP2A6 substrate interaction in males.

    更新日期:2018-09-26
  • Camptothecin enhances c-Myc-mediated endoplasmic reticulum stress and leads to autophagy by activating Ca2+-mediated AMPK
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-25
    Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi, Gi-Young Kim

    Camptothecin (CPT) from Camptotheca acuminate was discovered for anticancer drugs, which targets topoisomease I. However, whether CPT regulates c-Myc expression has not been understood in endoplasmic reticulum (ER) stress and autophagy. In this study, we found that CPT enhanced c-Myc expression and that the transient knockdown of c-Myc abrogated reactive oxygen species (ROS) generation, which resulted in the accumulation of ER stress-regulating proteins, such as PERK, eIF2α, ATF4, and CHOP. Moreover, the transfection of eIF2α-targeted siRNA attenuated CPT-induced autophagy and decreased the levels of Beclin-1 and Atg7, which indicated that CPT upregulated ER stress-mediated autophagy. In addition, CPT phosphorylated AMPK in response to intracellular Ca2+ release. Ca2+ chelators, ethylene glycol tetraacetic acid and a CaMKII inhibitor, K252a, decreased CPT-induced Beclin-1 and Atg7, and downregulated AMPK phosphorylation, which suggested that CPT-induced Ca2+ release leads to the activation of autophagy through CaMKII-mediated AMPK phosphorylation. CPT also phosphorylated JNK and activated the DNA-binding activity of AP-1; furthermore, knockdown of JNK abolished the expression level of Beclin-1 and Atg7, which implied that the JNK-AP-1 pathway was a potent mediator of CPT-induced autophagy. Our findings indicated that CPT promoted c-Myc-mediated ER stress and ROS generation, which enhances autophagy via the Ca2+-AMPK and JNK-AP-1 pathways.

    更新日期:2018-09-26
  • C. elegans Development and Activity Test detects mammalian developmental neurotoxins
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-25
    Piper Reid Hunt, Nicholas Olejnik, Keenan D. Bailey, Cory A. Vaught, Robert L. Sprando

    Due to the high cost and long duration of traditional testing methods for developmental neurotoxicity (DNT), only a small fraction of chemicals that humans are exposed to have been assessed for DNT activity. In order to ensure public safety, human-predictive methods for DNT detection that are faster and less resource intensive are urgently required. Using Caenorhabditis elegans, a novel worm Development and Activity test (wDAT) has been designed that uses a relatively inexpensive small-animal activity tracker and takes less than 4 days to complete. The wDAT was able to detect both developmental delay and hyperactivity for arsenic, lead, and mercury, heavy metals that are known human developmental neurotoxins and have been associated with hyperactivity in children. Lithium was also tested as a control developmental toxin that is not considered a mammalian neurotoxin. With the wDAT, lithium induced developmental delay but not hyperactivity. This initial assessment of a new assay for DNT detection indicates that the wDAT has potential for detecting at least some types of mammalian developmental neurotoxins. A planned 20-compound validation study will clarify the utility of the wDAT for predicitive toxicology.

    更新日期:2018-09-26
  • Subchronic toxicity evaluation of 5-hexenyl isothiocyanate, a nature identical flavoring substance from Wasabia japonica, in F344/DuCrj rats
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-25
    Jun-ichi Akagi, Young-Man Cho, Yasuko Mizuta, Takeshi Toyoda, Kumiko Ogawa

    5-Hexenyl isothiocyanate (5-HeITC) is a naturally derived flavoring substance from Wasabia japonica. To clarify the toxicological profile of 5-HeITC, we performed a subchronic toxicity study of 5-HeITC with intragastric administration at daily doses of 0, 3, 12, or 48 mg/kg body weight (BW) to 6-week-old male and female F344/DuCrj rats for 13 weeks. Body weight gain was decreased in the male 48 mg/kg BW group. Decreased triglycerides were observed in the male over 12 mg/kg BW and female 48 mg/kg BW groups. Decreased total cholesterol was observed in the male 48 mg/kg BW group. Increases in relative liver weights were observed in the male 48 mg/kg BW and female over 12 mg/kg BW groups. Increases in absolute and relative heart weights were observed in the female over 12 mg/kg BW groups. Simple hyperplasia in the urinary bladder was found in the male and female 12 mg/kg BW groups, and nodular hyperplasia was found in the female 48 mg/kg BW group. Based on these findings, the target organs of 5-HeITC were determined to be the urinary bladder, heart, and liver. The no-observed-adverse-effect level of 5-HeITC for both sexes was estimated to be 3 mg/kg BW.

    更新日期:2018-09-26
  • Protective effects of tricetinidin against oxidative stress inducers in rat kidney cells: A comparison with delphinidin and standard antioxidants
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-25
    Ezgi Eyluel Bankoglu, Jens Broscheit, Theresa Arnaudov, Norbert Roewer, Helga Stopper
    更新日期:2018-09-26
  • Comparative in vitro cytotoxicity of the emerging Fusarium mycotoxins beauvericin and enniatins to porcine intestinal epithelial cells
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-25
    Sophie Fraeyman, Evelyne Meyer, Mathias Devreese, Gunther Antonissen, Kristel Demeyere, Freddy Haesebrouck, Siska Croubels

    The emerging Fusarium mycotoxins beauvericin (BEA) and enniatin (ENN) A, ENN A1, ENN B and ENN B1 gain increasing interest due to their highly prevalent contamination of cereals and cereal products. After oral intake, the gastro-intestinal tract is the first possible site of interaction. In the present in vitro study, the relative cytotoxicity of these mycotoxins towards proliferating and differentiated intestinal porcine epithelial cells of the jejunum (IPEC-J2) was evaluated using flow cytometric viability analysis. IPEC-J2 cells showed the highest sensitivity to BEA and ENN A. In proliferating cells, incubation for 24h with 10 μM BEA caused complete disruption, while the viability percentage declined to 32% after 24h of incubation with 10 μM ENN A. ENN A1 and ENN B1 were less cytotoxic with 87% and 93% viable cells after 24h of incubation with 10 μM ENN A1 and B1, respectively. ENN B was the least cytotoxic since incubation at concentrations up to 100 μM resulted in 83% viable proliferating cells. The same trend was observed for differentiated cells. The limited in vitro cytotoxic effect of ENN B on intestinal cells corroborates previous in vivo findings in broiler chicken in which dietary ENN B had minimal effect on intestinal morphometry.

    更新日期:2018-09-26
  • In silico and in vitro prediction of the toxicological effects of individual and combined mycotoxins
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-26
    Mercedes Taroncher, Josefa Tolosa, Alessandra Prosperini, Maria-Jose Ruiz

    3-Acetyldeoxynivalenol (3-AcDON) and 15-acetyldeoxynivalenol (15-AcDON) are converted to deoxynivalenol (DON) in vivo and their simultaneous presence may increase DON intake. Mixtures of DON and its derivatives are a public health concern. In this study DON, 3-AcDON and 15-AcDON were evaluated in vitro and in silico. The in vitro cytotoxicity of DON and its derivatives individually and combined was determined by the Neutral Red (NR) assay in human hepatocarcinoma (HepG2) cells. The concentrations tested were from 1.25 to 15 μM (DON) and from 0.937 to 7.5 μM (DON derivatives). The IC50 values were from >15 to 2.55 μM (DON), from 1.77 to 1.02 μM (3-AcDON), and from 4.05 to 1.68 μM (15-AcDON). 3-AcDON was the most cytotoxic molecule in HepG2 cells. The concentrations tested in combinations ranged from 0.5625 to 4.5 μM (DON), and from 0.094 to 0.75 μM (DON derivatives), with ratios of 1:6 (DON+3-AcDON and DON+15-AcDON), 1:1 (3-AcDON+15-AcDON) and 1:6:6 (DON+3-AcDON+15-AcDON). The DON+15-AcDON mixture exhibited additive effects, while the rest showed synergistic effects. In silico methods assess individual mycotoxins. Absorption, Distribution, Metabolism, Excretion and Toxicity of mycotoxins were predicted using in silico SwissADME tools. Absorption, Distribution, Metabolism and Excretion profile prediction shows high gastrointestinal absorption and CYP3A4 mediated metabolism.

    更新日期:2018-09-26
  • 更新日期:2018-09-25
  • In vitro safety pharmacology evaluation of 2-hydroxybenzylamine acetate
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-22
    John C. Fuller, Lisa M. Pitchford, Ryan D. Morrison, J. Scott Daniels, Charles R. Flynn, Naji N. Abumrad, John A. Oates, Olivier Boutaud, John A. Rathmacher

    2-hydroxybenzylamine (2-HOBA), a compound found in buckwheat, is a potent scavenger of reactive γ-ketoaldehydes, which are increased in diseases associated with inflammation and oxidative stress. While the potential of 2-HOBA is promising, studies were needed to characterize the safety of the compound before clinical trials. In a series of experiments, the risks of 2-HOBA-mediated mutagenicity and cardio-toxicity were assessed in vitro. The effects of 2-HOBA on the mRNA expression of select cytochrome P450 (CYP) enzymes were also assessed in cryopreserved human hepatocytes. Further, the distribution and metabolism of 2-HOBA in blood were determined. Our results indicate that 2-HOBA is not cytotoxic or mutagenic in vitro and does not induce the expression of CYP1A2, CYP2B6, or CYP3A4 in human hepatocytes. The results of the hERG testing showed a low risk of cardiac QT wave prolongation. Plasma protein binding and red blood cell distribution characteristics indicate low protein binding and no preferential distribution into erythrocytes. The major metabolites identified were salicylic acid and the glycoside conjugate of 2-HOBA. Together, these findings support development of 2-HOBA as a nutritional supplement and provide important information for the design of further preclinical safety studies in animals as well as for human clinical trials with 2-HOBA.

    更新日期:2018-09-25
  • Rat feeding trials: A comprehensive assessment of contaminants in both genetically modified maize and resulting pellets
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-22
    S. Chereau, P. Rogowsky, B. Laporte, X. Coumoul, A. Moing, N. Priymenko, P. Steinberg, R. Wilhelm, J. Schiemann, B. Salles, F. Richard-Forget

    We analyzed a comprehensive set of contaminants in MON810 and NK603 genetically modified (GM) maize, and their non-GM counterparts, used in a rat feeding study (the GMO90 + project). Both the maize grains and the manufactured pellets were characterized. Only minor differences in contaminant levels between GM and corresponding non-GM harvests were evidenced. Fumonisin and deoxynivalenol mycotoxins were the pollutants present in the highest amounts, with concentrations that were however largely below acceptance reference values. Our data reporting slightly higher levels of fumonisin in MON810 compared to its non-GM counterpart corroborate the lower susceptibility of insect resistant Bt maize to fumonisin-producing fungi. Traces of glyphosate (0.016 mg/kg) were evidenced in grains from NK603 treated crops. Regarding the pellets, analysis of more than 650 potentially toxic substances revealed low amounts of various mycotoxins, pesticides and heavy metals. Concentrations of contaminants quantified in the pellets were however far below the maximum level of residues values set by regulatory agencies, and no substantial differences in contaminants between GM and non-GM pellets were observed. Moreover, when comparing the contamination status of grains and pellets, we demonstrate yet again that characterizing the grains is actually not sufficient to foresee the quality of the produced pellets.

    更新日期:2018-09-25
  • Biological markers of harm can be detected in mice exposed for two months to low doses of Third Hand Smoke under conditions that mimic human exposure
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-22
    Yuxin Chen, Neema Adhami, Manuela Martins-Green

    Third-hand smoke (THS) is a recently discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces of environments where smoking has occurred. Our objective was to determine whether there is a dose-dependent effect of THS exposure on biological markers of harm (BMH) using an in vivo exposure system that mimics exposure of humans to THS. THS exposure generated from as low as the 10 cigarettes-smoking regimen, resulted in increased circulating inflammatory cytokines, tumor necrosis factor alpha, interleukin 1 alpha, and granulocyte macrophage colony-stimulating factor. We also found that there was an increase in adrenocorticotropic hormone and superoxide dismutase and a decrease in ATP levels in liver tissue. Many of the altered BMH that are related to oxidative stress and decrease in ATP levels, suggest mitochondrial dysfunction. THS exposure generated from the 20 and 40 cigarettes-smoking regimen resulted in further damage. Our studies are important because virtually nothing is known about the physiological damage caused by different levels of THS exposure. These studies can also serve to educate the public on the dangers of THS and the BMH we identified can potentially be used in the clinic, once verified in exposed humans.

    更新日期:2018-09-25
  • Assessing the combined toxicity of the natural toxins, aflatoxin B1, fumonisin B1 and microcystin-LR by high content analysis
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-22
    Julie P. Meneely, Jana Hajšlová, Rudolf Krska, Christopher T. Elliott
    更新日期:2018-09-25
  • Fusarium mycotoxins and in vitro species-specific approach with porcine intestinal and brain in vitro barriers: A review
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-22
    A. Bertero, L.J. Spicer, F. Caloni

    Fusarium mycotoxins, such as fumonisins, trichothecenes, zearalenone and emerging fusariotoxins, common contaminants of feed and food, have received increased interest, due to the possible impact on animal and human health.In this context, it is urgent to focus our attention on fusariotoxins adverse effects, considering and analysing data in relation to their species-specificity.The in vitro approach for fusariotoxins risk assessment evaluation, through porcine epithelial barriers model, allowed to collect information on their absorption profile, bioavailability and toxicity.The aim of this review is to give an overview on Fusarium mycotoxins and their interactions with porcine intestinal and brain in vitro barriers, because they represent direct target organs of toxicity and as tools to evaluate their permeability and transport.

    更新日期:2018-09-25
  • Curcumin prevents potassium dichromate (K2Cr2O7)-induced renal hypoxia
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-21
    Sabino H. Avila-Rojas, Edilia Tapia, Alfredo Briones-Herrera, Omar E. Aparicio-Trejo, Juan C. León-Contreras, Rogelio Hernández-Pando, José Pedraza-Chaverri

    Curcumin exhibits several therapeutic properties. Potassium dichromate (K2Cr2O7)-induced nephropathy is associated with oxidative stress. Reactive oxygen species production affects renal oxygenation that may participate in the progression of renal damage. The aim of the present work was to elucidate whether K2Cr2O7-induced nephropathy is associated to partial O2 pressure (pO2) impairment and if curcumin is able to prevent it. Four groups of rats were studied: control group; K2Cr2O7 group (12.5 mg/kg, s.c.); curcumin + K2Cr2O7 group, in which animals were treated with curcumin (400 mg/kg/day, p.o.) for 10 days before K2Cr2O7 injection; and curcumin group. All animals were sacrificed 48 h after the end of the treatments. K2Cr2O7 administration increased renal function markers and decreased glomerular filtration rate, pO2 and renal perfusion. Concerning hemodynamic parameters, K2Cr2O7 increased mean arterial pressure and renal vascular resistance and reduced renal blood flow. The hemodynamic changes were attributed to decreased availability of nitric oxide and increased 3-nitrotyrosine levels. Moreover, increased superoxide anion production and vascular endothelial growth factor levels were observed after K2Cr2O7 administration. Curcumin attenuated all the above-described alterations. Our results suggest that the protective effects of curcumin in K2Cr2O7-induced nephropathy are associated with its ability to prevent O2 supply reduction.

    更新日期:2018-09-22
  • Toxicological effects of fumonisin B1 in combination with other Fusarium toxins
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-21
    Jessica Audrey Feijó Corrêa, Paloma Bianca Orso, Keliani Bordin, Raquel Vaz Hara, Fernando Bittencourt Luciano
    更新日期:2018-09-22
  • Cytogenetic and genotoxic effects of Rosmaniric Acid on Allium cepa L. root meristem cells
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-21
    Recep Liman, İbrahim Hakkı Ciğerci, Süleyman Gökçe
    更新日期:2018-09-22
  • NRF2 mitigates acute alcohol-induced hepatic and pancreatic injury in mice
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-21
    Jing Sun, Jingqi Fu, Yang Zhong, Lu Li, Chengjie Chen, Xiaolei Wang, Linlin Wang, Yongyong Hou, Huihui Wang, Rui Zhao, Xixuan Zhang, Masayuki Yamamoto, Yuanyuan Xu, Jingbo Pi

    Binge alcohol drinking is an important health concern and well-known risk factor for the development of numerous disorders. Oxidative stress plays a critical role in the pathogenesis of acute alcoholism. Nuclear factor erythroid 2 like 2 (NRF2) is a master regulator of cellular adaptive response to oxidative insults. However, the role of NRF2 in acute alcoholism and associated pathologies remains unclear. We found that Nrf2-knockout (Nrf2-KO) mice had exaggerated hypoglycemia and hypothermia and increased mortality compared to wildtype mice after binge ethanol exposure. This phenotype was partially rescued by providing warm environment and/or glucose administration. Acute high dose of alcohol exposure resulted in substantially worsened liver and pancreatic injuries in Nrf2-KO mice. Importantly, deficiency of Nrf2 allowed severe pancreatitis and pancreatic β-cell injury with increased insulin secretion and/or leaking during binge ethanol exposure, which contributed to hypoglycemia. In contrast, a clinically used NRF2 activator dimethyl fumarate (DMF) protected against hypoglycemia and lethality induced by acute ethanol exposure. Furthermore, Nrf2-KO mice likely had defective hepatic acetaldehyde metabolism. Taken together, NRF2 plays an important protective role against acute binge alcohol-induced hepatic and pancreatic damage, which may be partially attributable to its primary regulating role in antioxidant response and impact on ethanol metabolism.

    更新日期:2018-09-22
  • The role of mycotoxins in the human exposome: Application of mycotoxin biomarkers in exposome-health studies
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-21
    Sonia Marín, German Cano-Sancho, Vicente Sanchis, Antonio J. Ramos

    Mycotoxins are secondary metabolites produced by fungi that may contaminate different foods intended for human consumption, resulting in a widespread exposure worldwide. The novel exposome paradigm has the ambition to decipher the different environmental insults threating human health throughout the entire lifespan. Given the large potential impact of mycotoxins in terms of human exposure and related health effects, the ambition of this review is to present this group of chemical compounds and the high interest to be included in exposome projects. Furthermore, we also attempt to approach the novel exposome paradigm to more traditional disciplines such as mycotoxin exposure assessment and mycotoxicology, introducing the new methodological challenges and translational needs. Hence, we provide an overview of major biomarkers currently developed, biological matrices where these may be found, an overview of internal exposure levels and potential co-occurrence with environmental chemicals and finally an overview of major health effects with the illustrative example of the potent xenoestrogen zearalenol. Conversely, these new approaches may be an excellent opportunity to fill many research gaps on mycotoxins research as the identification of associations with human health, elucidation of join effect with other environmental exposures or the decipher of underlying molecular mechanisms by using advanced OMICs technologies.

    更新日期:2018-09-22
  • Soy-deficient diet induces renal lesions in juvenile rats
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-21
    Eli Parker, Pallavi McElroy, Catherine Picut, Kathleen Szabo, Stephanie White-Hunt

    Certified LabDiet® 5K96 Advanced Protocol™ Verified Casein Diet 10 IF (5K96) is a commercial diet low in soy isoflavones developed for use in developmental and reproductive toxicity (DART) studies, especially those designed to detect endocrine disruptors. The objective of this study was to determine the incidences and severities of 5K96-associated renal lesions in control F0 and F1 cohorts of rats fed the 5K96 diet. Kidneys from control animals of four DART studies involving Sprague-Dawley rats fed the 5K96 diet, were evaluated microscopically. Mineralization and basophilic tubules were present in high incidence/severity in males and females compared to historical controls fed conventional diets. F1 cohorts were affected to a far greater degree than F0 cohorts, and females were affected more than males. Consideration of target tissue and mode of action should be given before automatically incorporating the 5K96 diet into DART study designs, and caution should be exercised when identifying and interpreting renal toxicity in the F1 cohorts of such studies.

    更新日期:2018-09-21
  • Comparative in vitro studies of the biological potential and chemical composition of stems, leaves and berries Aronia melanocarpa's extracts obtained by subcritical water extraction
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-21
    Aleksandra Cvetanović, Gokhan Zengin, Zoran Zeković, Jaroslava Švarc-Gajić, Slavica Ražić, Ana Damjanović, Pavle Mašković, Milan Mitić

    Preparation of functional products as well as natural-based products requires non-toxic but effective extraction techniques. In this study, subcritical water extraction was used for the extraction of different aronia parts in order to explore their potential. Stems, leaves and berries of Aronia melanocarpa were extracted under the following conditions: temperature 130 °C; pressure 35 bar; time 20 min. The total phenols and flavonoid contents of the produced extracts were evaluated by conventional spectrophotometric methods. Additionally, the main phenolic compounds were also identified and quantified by high performance liquid chromatography with diode array detection (HPLC-DAD). The biological potential of the extracts was evaluated by determining their antioxidant (DPPH, ABTS and lipid peroxidation assays), antimicrobial, enzyme inhibitory (cholinesterase and elastase) and cytotoxic effects (HeLa, A-549, LS-174T, MRC-5 cell lines). The results indicate that leaves and berries extracts exhibited stronger antioxidant action when compared with stems. The strongest cholinesterase and elastase inhibitory activity was also found in berries extract. Similarly, the extracts obtained from leaves and berries showed considerable cytotoxic effects against tested cell lines. A moderate antimicrobial effects was observed too. Demonstrated biological potential of all three aronia parts can trace a new road map for developing newly designed functional products.

    更新日期:2018-09-21
  • Review article: Role of satiety hormones in anorexia induction by ttrichothecene mycotoxins
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-20
    Chloé Terciolo, Marc Maresca, Philippe Pinton, Isabelle P. Oswald

    The trichothecenes, produced by Fusarium, contaminate animal feed and human food in all stages of production and lead to a large spectrum of adverse effects for animal and human health. An hallmark of trichothecenes toxicity is the onset of emesis followed by anorexia and food intake reduction in different animal species (mink, mice and pig). The modulation of emesis and anorexia can result from a direct action of trichothecenes in the brain or from an indirect action in the gastrointestinal tract. The direct action of trichothecenes involved specific brain areas such as nucleate tractus solitarius in the brainstem and the arcuate nuclei in the hypothalamus. Activation of these areas in the brain leads to the activation of specific neuronal populations containing anorexigenic factors (POMC and CART). The indirect action of trichothecenes in the gastrointestinal tract involved, by enteroendocrine cells, the secretion of several gut hormones such as cholecystokinin (CCK) and peptide YY (PYY) but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP) and 5-hydroxytryptamine (5-HT), which transmitted signals to the brain via the gut-brain axis. This review summarizes current knowledge on the effects of trichothecenes, especially deoxynivalenol, on emesis and anorexia and discusses the mechanisms underlying trichothecenes-induced food reduction.

    更新日期:2018-09-21
  • Apoptotic cell death induced by Z-Ligustilidein human ovarian cancer cells and role of NRF2
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-20
    Fangfang Lang, Jinfeng Qu, Haiqin Yin, Lanyu Li, Yuanyuan Zhi, Yanping Liu, Zhenghui Fang, Enkui Hao

    Z-Ligustilide is the most potent bioactive component of Angelica sinensis, which is widely used in Chinese traditional medicine. Z-Ligustilide selectively affected ovarian cancer cell survival in a dose dependent manner. Z-Ligustilide induced apoptotic cell death was determined by flow cytometry. We also demonstrated that apoptotic cell death was triggered by Z-Ligustilideinduced oxidative stress and mitochondria played an active role. Mitochondrial polarization was reduced by Z-Ligustilidewhereas mitochondrial superoxide formation was increased. NRF2 was induced by Z-Ligustilide in OVCAR-3 cells at epigenetic level and its downstream antioxidant defense genesHeme oxygenase-1,NAD(P)H Quinone Dehydrogenase 1, UDP Glucuronosyltransferase Family 1 Member A1and Glutamate-Cysteine Ligase. NRF2 knockdown by siRNA resulted increased cell death by Z-Ligustilide in ovarian cancer cells. Our result demonstrated the pro-survival role of NRF2 in Z-Ligustilide induced ovarian cancer cell death.

    更新日期:2018-09-20
  • Brazil nut improves the oxidative metabolism of superoxide-hydrogen peroxide chemically-imbalanced human fibroblasts in a nutrigenomic manner
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-20
    Karen Lilian Schott, Charles Elias Assmann, Cibele Ferreira Teixeira, Aline Augusti Boligon, Samuel Rodrigo Waechter, FabioAndrei Duarte, Euler Esteves Ribeiro, Ivana Beatrice Mânica da Cruz
    更新日期:2018-09-20
  • Xanthohumol inhibits cell proliferation and induces apoptosis in human thyroid cells
    Food Chem. Toxicol. (IF 3.977) Pub Date : 2018-09-18
    Daniel O. Carvalho, Jaime Freitas, Patrícia Nogueira, Sónia N. Henriques, Alexandre M. Carmo, Mónica A. Castro, Luís F. Guido
    更新日期:2018-09-19
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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