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  • New grapefruit cultivars exhibit low cytochrome P4503A4-Inhibition activity
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-20
    Yelena Guttman; Iris Yedidia; Adi Nudel; Yuliya Zhmykhova; Zohar Kerem; Nir Carmi

    Furanocoumarins are the main compounds responsible for the food–drug interactions known as the grapefruit effect, which is caused by the inhibition of CYP3A4-mediated drug metabolism. We evaluated the effects of two new, low-furanocoumarin grapefruit cultivars on CYP3A4 activity and the roles of different furanocoumarins, individually and together with other juice compounds, in the inhibition of CYP3A4 by grapefruit. Whereas a standard grapefruit cultivar inhibited CYP3A4 activity in a dose-dependent manner, neither of the two examined low-furanocoumarin cultivars had an inhibitory effect. Despite the fact that bergamottin and 6′,7′-dihydroxybergamottin are weak inhibitors of CYP3A4, their relatively high levels in grapefruit make them the leading cause of the grapefruit effect. We found that furanocoumarins together with other juice compounds inhibit CYP3A4 in an additive manner. In silico docking simulation was employed, and differentiated between high- and low-potency inhibitors, suggesting that modeling may be useful for identifying potentially harmful food–drug interactions.

    更新日期:2020-01-21
  • Inflammation: Cause or consequence of chronic cholestatic liver injury
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-20
    Benjamin L. Woolbright

    Cholestasis is a result of obstruction of the biliary tracts. It is a common cause of liver pathology after exposure to toxic xenobiotics and during numerous other liver diseases. Accumulation of bile acids in the liver is thought to be a major driver of liver injury during cholestasis and can lead to eventual liver fibrosis and cirrhosis. As such, current therapy in the field of chronic liver diseases with prominent cholestasis relies heavily on increasing choleresis to limit accumulation of bile acids. Many of these same diseases also present with autoimmunity before the onset of cholestasis though, indicating the inflammation may be an initiating component of the pathology. Moreover, cytotoxic inflammatory mediators accumulate during cholestasis and can propagate liver injury. Anti-inflammatory biologics and small molecules have largely failed clinical trials in these diseases though and as such, targeting inflammation as a means to address cholestatic liver injury remains debatable. The purpose of this review is to understand the different roles that inflammation can play during cholestatic liver injury and attempt to define how new therapeutic targets that limit or control inflammation may be beneficial for patients with chronic cholestatic liver disease.

    更新日期:2020-01-21
  • The curcumin analogue WZ35 affects glycolysis inhibition of gastric cancer cells through ROS-YAP-JNK pathway
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-17
    Tongke Chen; Liqian Zhao; Shinuo Chen; Bin Zheng; Hong Chen; Tianni Zeng; Hanxiao Sun; Sijia Zhong; Wencan Wu; Xiaokun Lin; Lihua Wang
    更新日期:2020-01-21
  • Development of TPGS/F127/F68 mixed polymeric micelles: Enhanced oral bioavailability and hepatoprotection of syringic acid against carbon tetrachloride-induced hepatotoxicity
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-16
    Congyong Sun; Wenjing Li; Ping Ma; Yang Li; Yuan Zhu; Huiyun Zhang; Michael Adu-Frimpong; Wenwen Deng; Jiangnan Yu; Ximing Xu
    更新日期:2020-01-16
  • Bisphenol A exposure is involved in the development of Parkinson like disease in Drosophila melanogaster
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-14
    Elize Aparecida Santos Musachio; Stífani Machado Araujo; Vandreza Cardoso Bortolotto; Shanda de Freitas Couto; Mustafa Munir Mustafa Dahleh; Marcia Rósula Poetini; Eliana Fernandes Jardim; Luana Barreto Meichtry; Bruna Piaia Ramborger; Rafael Roehrs; Gustavo Petri Guerra; Marina Prigol
    更新日期:2020-01-14
  • 更新日期:2020-01-14
  • A method to assess lifetime dietary risk: Example of cadmium exposure
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-13
    Manon Pruvost-Couvreur; Bruno Le Bizec; Camille Béchaux; Gilles Rivière

    Usually health risk related to food contaminants is assessed based on consumption data collected on a few days. Consequently, this approach considers neither the evolution of exposures over time nor the potential accumulation of the substance. The aim of the present study was to develop a method to assess lifetime dietary risk due to cadmium exposure. Three methods were compared, respectively based on age, dietary pattern and sociodemographic characteristics. Additionally, exposure trajectories were converted into cadmium body burden trajectories using a PBTK-TD model ultimately predicting the occurrence of renal effects. It was shown that dietary exposures to cadmium, as well as exceedances of health based guidance values, greatly vary with age and individual profiles. The developed methods allowed identifying parameters affecting dietary exposure to cadmium and distinguishing at-risk subpopulations. Furthermore, this study demonstrated that it is necessary to consider individual changes through life and kinetic of the substance to assess risk properly.

    更新日期:2020-01-13
  • Subchronic feeding toxicity studies of drought-tolerant transgenic wheat MGX11-10 in Wistar Han RCC rats
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-11
    Yinghua Liu; Shujing Zhang; Qinghong Zhou; Shufei Li; Jing Zhang; Li Zhang; Shuqing Jiang; Qian Zhang; Xiaoli Zhou; Chao Wu; Qing Gu; Zhi Yong Qian

    A subchronic toxicity study were conducted in Wistar Han RCC rats to evaluate the potential health effects of genetically modified (GM), drought-tolerant wheat MGX11-10. Rats were fed a rodent diet formulated with MGX11-10 and were compared with rats fed a diet formulated with its corresponding non-transgenic control Jimai22 and rats fed a basal diet. MGX11-10 and Jimai22 were ground into flour and formulated into diets at concentrations of 16.25, 32.5, or 65%, w/w% and fed to rats (10/sex/group) for 13 weeks. Compared with rats fed Jimai22 and the basal-diet group, no biologically relevant differences were observed in rats fed the GM diet with respect to body weight/gain, food consumption/efficiency, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, clinical chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, the MGX11-10 diets did not cause any treatment-related effects in rats following at least 90 days of dietary administration as compared with rats fed diets with the corresponding non-transgenic control diet and the basal-diet group. The MGX11-10 diets are considered equivalent to the diets prepared from conventional comparators. The results demonstrated that MGX11-10 wheat is as safe and wholesome as the corresponding non-transgenic control wheat.

    更新日期:2020-01-13
  • Part I. polyphenols composition and antioxidant potential during ‘Blaufränkisch’ grape maceration and red wine maturation, and the effects of trans-resveratrol addition
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-11
    Nataša Poklar Ulrih; Rok Opara; Mihaela Skrt; Tatjana Košmerl; Mojmir Wondra; Veronika Abram
    更新日期:2020-01-11
  • Part II. Influence of trans-resveratrol addition on the sensory properties of ‘Blaufränkisch’ red wine
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-10
    Nataša Poklar Ulrih; Rok Opara; Mojca Korošec; Mojmir Wondra; Veronika Abram
    更新日期:2020-01-11
  • A strategy for test article selection and phytochemical characterization of Echinacea purpurea extract for safety testing
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-10
    Suramya Waidyanatha; Jessica Pierfelice; Tim Cristy; Esra Mutlu; Brian Burback; Cynthia V. Rider; Kristen Ryan

    Botanical dietary supplements (BDS) are used around the world for many purported therapeutic properties. The selection of an authentic product and it's phytochemical characterization is critical to generate robust safety data. Because botanicals are complex mixtures with variable quality, identification of a representative product for testing has been challenging. Echinacea is used for its purported immune stimulant properties and was listed as the 2nd top-selling BDS in 2018. However, there are limited safety data for Echinacea. Hence, the National Toxicology Program (NTP) has selected Echinacea for safety testing using rodent models. Here, we describe selection and comprehensive characterization of an Echinacea purpurea root extract to be used in the NTP testing program. Using non-targeted chemical analyses combined with chemometric analysis, a potential unfinished product (i.e., an extract that serves as source material for finished products) of Echinacea purpurea was selected. The product was then authenticated using chemical and DNA techniques and characterized, including the phytochemical composition. Among numerous constituents identified, caftaric acid, chicoric acid, chlorogenic acid and dodeca-2(E),4(E),8(Z),10(E/Z)-tetraenoic acid isobutylamide made up a small fraction of the extract. Based on these analyses, an approach is proposed for test article selection for Echinacea research which can be adapted to other botanicals.

    更新日期:2020-01-11
  • Molecular modelling methods in food safety: Bisphenols as case study
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-10
    Francesca Cavaliere; Stefano Lorenzetti; Pietro Cozzini
    更新日期:2020-01-11
  • Alternative toxicological methods for establishing residue definitions applied for dietary risk assessment of pesticides in the European Union
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-10
    Katarzyna Czaja; Paweł Struciński; Wojciech Korcz; Maria Minorczyk; Agnieszka Hernik; Bożena Wiadrowska
    更新日期:2020-01-11
  • Assessment of Tetrabromobisphenol and Hexabromocyclododecanes exposure and risk characterization using occurrence data in foods
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-10
    Joon-Goo Lee; Youngjin Jeong; Dongsul Kim; Gil-Jin Kang; Youngwon Kang

    Tetrabromobisphenol A (TBBPA) and Hexabromocyclododecanes (HBCDs) are two of the most used BFRs and they have cumulated in the environment. TBBPA and HBCDs in food were determined and their risks were assessed. The analytical method used was validated in different food categories, and the performance parameters were acceptable based on the criteria of AOAC. Fish and cephalopods were contaminated with TBBPA higher than other foods, and fish contained higher levels of HBCDs than other foods. α-HBCD was the predominant diastereomer in fish and meat and had strong correlations with HBCDs in fish and cephalopods. HBCDs accumulated easier than TBBPA in food. People were exposed to TBBPA from 0.125 ng kg−1 b.w. day−1 to 0.284 ng kg−1 b.w. day−1 and HBCDs from 0.353 ng kg−1 b.w. day−1 to 1.006 ng kg−1 b.w. day−1 via food and air. Food mainly contributed to exposure to TBBPA and HBCDs and vegetables were the main contributors for exposure to TBBPA and HBCDs in food. MOEs for the whole population were over 100, and the risks of exposure to TBBPA and HBCDs from food and the environment were of low concern to public health.

    更新日期:2020-01-11
  • Dose addition in chemical mixtures inducing craniofacial malformations in zebrafish (Danio rerio) embryos
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-09
    Maria Zoupa; Edwin P. Zwart; Eric R. Gremmer; Ananditya Nugraha; Sharon Compeer; Wout Slob; Leo T.M. van der Ven

    A challenge in cumulative risk assessment is to model hazard of mixtures. EFSA proposed to only combine chemicals linked to a defined endpoint, in so-called cumulative assessment groups, and use the dose-addition model as a default to predict combined effects. We investigated the effect of binary mixtures of compounds known to cause craniofacial malformations, by assessing the effect in the head skeleton (M-PQ angle) in 120hpf zebrafish embryos. We combined chemicals with similar mode of action (MOA), i.e. the triazoles cyproconazole, triadimefon and flusilazole; next, reference compounds cyproconazole or triadimefon were combined with dissimilar acting compounds, TCDD, thiram, VPA, prochloraz, fenpropimorph, PFOS, or endosulfan. These mixtures were designed as (near) equipotent combinations of the contributing compounds, in a range of cumulative concentrations. Dose-addition was assessed by evaluation of the overlap of responses of each of the 14 tested binary mixtures with those of the single compounds. All 10 test compounds induced an increase of the M-PQ angle, with varying potency and specificity. Mixture responses as predicted by dose-addition did not deviate from the observed responses, supporting dose-addition as a valid assumption for mixture risk assessment. Importantly, dose-addition was found irrespective of MOA of contributing chemicals.

    更新日期:2020-01-09
  • Katja Parschat: Conceptualization, Project administration, Writing - Review & Editing, Anne Oehme: Data curation, Writing - original draft, Jost Leuschner: Methodology, Investigation, Stefan Jennewein: Conceptualization, Supervision, Julia Parkot: Conceptualization, Project administration, Writing - review & editing, SupervisionA safety evaluation of mixed human milk oligosaccharides in rats
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-07
    Katja Parschat; Anne Oehme; Jost Leuschner; Stefan Jennewein; Julia Parkot

    Human milk oligosaccharides (HMOs) are indigestible carbohydrates representing the third largest fraction of solutes in human breastmilk. They provide valuable prebiotic and anti-pathogenic functions in breastfed infants, but are not yet included in most infant formula products. Recent biotechnological advances now facilitate large-scale production of HMOs, providing infant formula manufacturers with the ability to supplement their products with HMOs to mimic human breastmilk. Although the safety of individual HMOs has been confirmed in preclinical toxicological studies, the safety of HMO mixtures has not been tested. We therefore performed bacterial reverse mutation and in vitro micronucleus tests and conducted a repeated-dose oral toxicity study in rats with a mixture of five HMOs (HMO MIX I), containing 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). HMO MIX I was not genotoxic and did not induce adverse effects in the repeated dose study. The no-observed-adverse-effect-level (NOAEL) for HMO MIX I in this study is 10% in the diet (equivalent to 5.67 g HMO MIX I/kg bw/day for males and 6.97 g HMO MIX I/kg bw/day for females). Our results provide strong evidence for the safety of HMO MIX I in infant products and general foods.

    更新日期:2020-01-07
  • Pyrrolizidine alkaloids in food and phytomedicine: Occurrence, exposure, toxicity, mechanisms, and risk assessment - A review
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-03
    Dieter Schrenk; Lan Gao; Ge Lin; Catherine Mahony; Patrick P.J. Mulder; Ad Peijnenburg; Stefan Pfuhler; Ivonne M.C.M. Rietjens; Lukas Rutz; Barbara Steinhoff; A. These

    Among naturally occurring plant constituents, the 1,2-unsaturated pyrrolizidine alkaloids (in the following termed ‘PAs’) play a distinct role because of the large number of congeners occurring in nature and the pronounced toxicity of some congeners. Several PAs are hepatotoxic in humans, experimental and farm animals and were shown to be potent hepatocarcinogens in laboratory rodents. Although the general mode of action leading to toxicity has been elucidated, i.e., being mediated by metabolic conversion of the parent molecule into a highly reactive electrophile capable of attacking cellular target molecules, major questions related to the risk assessment of PAs remain unresolved. It was the aim of a workshop held in September 2018 to shed more light on the occurrence, exposure, mode of action, toxicokinetics and –dynamics of PAs to improve the scientific basis for an advanced toxicological risk assessment. The contributions in nine chapters describe the scientific progress using advanced analytical methods, studies in subcellular fractions, cell culture, experimental animals and humans and the use of PBPK modeling and structure-activity relationship considerations aiming at a better understanding of PA toxicity and genotoxicity. Since PAs differ considerably in their toxic potencies and substantial species differences in sensitivity towards PA exposure exist, a special emphasis was placed on these issues.

    更新日期:2020-01-04
  • 更新日期:2020-01-04
  • Immunotoxicity and allergenic potential induced by topical application of perfluorooctanoic acid (PFOA) in a murine model
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-03
    Hillary L. Shane; Rachel Baur; Ewa Lukomska; Lisa Weatherly; Stacey E. Anderson

    Perfluorooctanoic acid (PFOA) is a per- and polyfluoroalkyl substance (PFAS) once used as a surfactant in the polymerization of chemicals. Because of its ubiquitous nature and long half-life, PFOA is commonly detected in the environment, wildlife, and humans. While skin exposure to PFOA is of concern, studies evaluating the immunotoxicity of dermal exposure are lacking. These studies evaluated the immunotoxicity of PFOA (0.5–2% w/v, or 12.5–50 mg/kg/dose) following dermal exposure using a murine model. PFOA (0.5–2%) was not identified to be an irritant or sensitizer using the local lymph node assay. The IgM antibody response to sheep red blood cell. was significantly reduced in the spleen following 4-days of dermal exposure (2%). PFOA exposure produced a significant decrease in thymus (1 and 2%) and spleen (0.5–2%) weight along with an increase in liver weight (0.5–2%). Immune cell phenotyping identified a reduction in the frequency (1 and 2%) and number (0.5–2%) of splenic B-cells. To further define the mechanism of immunotoxicity, gene expression was also evaluated in the skin. The findings support a potential involvement of the nuclear receptor PPARα. These results demonstrate that dermal exposure to PFOA is immunotoxic and raise concern about potential adverse effects from dermal exposure.

    更新日期:2020-01-04
  • Mitochondrial transcriptional study of the effect of aflatoxins, enniatins and carotenoids in vitro in a blood brain barrier model
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-02
    M. Alonso-Garrido; P. Tedeschi; A. Maietti; G. Font; N. Marchetti; L. Manyes

    C. maxima (var. Delica), a variety of pumpkin, is well known for its high concentration on carotenoids, possessing dietary benefits and antioxidant properties. Aflatoxins and enniatins are common mycotoxins present in food and feed with an extended toxicity profile in humans and animals. Both types of substances reach a wide range of tissues and organs and have the capability to penetrate the blood brain barrier. Since carotenoids and mycotoxins have been reported to modify diverse mitochondrial processes individually, transcriptional in vitro studies on human epithelial cells ECV 304 were conducted to analyze the relative expression of 13 mitochondria related genes. ECV 304 cells were differentiated for 9 days and treated for 2 h with: a) pumpkin (500 nM); b) aflatoxins (100 nM); c) enniatins (100 nM); d) aflatoxins (100 nM) and pumpkin (500 nM); e) enniatins (100 nM) and pumpkin (500 nM). Even at low concentrations, dietary carotenoids activity on mitochondrial genes expression reported a beneficial effect and, for most of the genes studied across the Electron Transport Chain (ETC), developed a protective effect when mixed with aflatoxins (AFs) or enniatins (ENs).

    更新日期:2020-01-02
  • Parameters for discrimination between organic and conventional production: A case study for chicory plants (Cichorium intybus L.)
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2020-01-02
    Lovro Sinkovič; Marijan Nečemer; Nives Ogrinc; Dragan Žnidarčič; David Stopar; Rajko Vidrih; Vladimir Meglič

    Organic crop production has become a highly attractive way of production over the world and thus the need for robust analytical techniques for their authentication. The main aim of this study is to identify appropriate biomarkers to discriminate between organic and conventionally grown chicory. Chicory is an appreciated leafy vegetable among producers and consumers, especially due to its undemanding cultivation and content of bioactive substances. Six different fertility management practices (control, two organic, two mineral, and a combination of organic and mineral fertilizers) were used to produce five chicory cultivars in a glasshouse pot experiment. Analysis of bioactive compounds, nitrogen assimilation, multi-elemental profiling and stable isotope ratio determination of carbon (C), nitrogen (N) and sulphur (S) were performed to differentiate between organic and conventional production. In this study, nitrogen isotopes are found to be an excellent way of identifying organically produced chicory of a different variety with the highest δ15N values. Conversely, the same samples had the lowest δ34S values indicating that also stable isotopes of S could be used as a marker for the authentication of organic production.

    更新日期:2020-01-02
  • Occurrence and potential health risks assessment of polycyclic aromatic hydrocarbons (PAHs) in different tissues of bivalves from Hainan Island, China
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-31
    Haihua Wang; Wei Huang; Ying Gong; Chienmin Chen; Tengyun Zhang; Xiaoping Diao

    The levels of 16 PAHs were determined in the adductor, gills, gonads, hepatopancreas and mantles of the pearl oyster (Pinctada martensii) and the mussel (Perna viridis) collected from coasts of Li'an and Xincun Bays. The levels of ΣPAHs ranged from 597.1 to 2332 ng g−1 d w in the various tissues of bivalves. The pyrolytic source played an important role in the local coastal environment. Significantly higher levels of M-PAHs and H-PAHs were observed in Pinctada martensii than in Perna viridis. The ΣPAHs at different tissues showed the following order from high to low: mantles > hepatopancreas > gonads > gills > adductor. When levels of individual PAHs in the five bivalve tissues have been compared with each other, high correlations have been found (r2 = 0.793–0.975). A general trend was observed that log transformed BSAFs declined with increase of Kow values. The estimated amount of ΣPAHs via ingestion of oyster and mussel varied from 1.35 × 10−2-1.70 × 10−1 and 2.15 × 10−2-1.91 × 10−1 μg kg−1 body weight day−1, respectively. The THQs and CRs calculated for regular consumption of raw bivalves were in the acceptable ranges and may not pose health risk concerns. But for certain population with higher consumption rate for PAHs contaminated bivalves, cautions should be taken for their higher cancer risk.

    更新日期:2019-12-31
  • Hazard assessment of small-size plastic particles: is the conceptual framework of particle toxicology useful?
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-30
    Frederikke Emilie Heddagaard; Peter Møller

    Humans are exposed to plastic particles, but there are no studies on environmental plastics in cell cultures or animals. The toxicological understanding arises from model particles like polystyrene, polyethylene or non-plastic particles like food-grade titanium dioxide. The majority of studies on polystyrene particles show toxicological effects on measures of oxidative stress, inflammation, mitochondrial dysfunction, lysosomal dysfunction and apoptosis. The toxic effects in cell cultures mainly occur at high concentrations. Polyethylene particles seem to generate inflammatory reactions, whereas other toxicological effects have not been assessed. There are very few studies on effects of polystyrene particles in animal models and these have not demonstrated overt indices of toxicity. Studies in animals are the likely way for hazard assessment of micro- or nanoplastics. However, co-culture systems that mimic the complex architecture of mammalian tissues can cost-efficiently determine the hazards of micro- and nanoplastics. Future studies should include low doses of micro- and nanoplastic particles, which are more relevant in the assessment of health risk than the extrapolation of effects from high doses to realistic doses. Based on studies on model particles, environmental exposure to micro- and nanoplastic particles may be a hazard to human health.

    更新日期:2019-12-31
  • Rapid determination of the free and total hydroxytyrosol and tyrosol content in extra virgin olive oil by stable isotope dilution analysis and paper spray tandem mass spectrometry
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-30
    Lucia Bartella; Fabio Mazzotti; Giovanni Sindona; Anna Napoli; Leonardo Di Donna

    A rapid analytical method for the determination of phenylethanoids content in extra virgin olive oil has been developed. The method intends to address the European regulation EU 432/2012 on health claims, which allows to report on the front label of olive oil, the positive health effects due to the consumption of this food. The innovative method is based on paper spray tandem mass spectrometry using deuterated standards. It relies on a two-step analysis, needed to assess the free form of tyrosol and hydroxytyrosol and their ester conjugates after hydrolysis treatment. Different olive oil samples have been analyzed and the classical analytical parameters such as accuracy, LOQ and LOD were calculated from fortified samples. The good values of the latters show the reliability of the new approach, that limits the time of analysis and sample preparation to few minutes.

    更新日期:2019-12-31
  • Overview of cisplatin-induced neurotoxicity and ototoxicity, and the protective agents
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-28
    Neife Aparecida Guinaim dos Santos; Rafaela Scalco Ferreira; Antonio Cardozo dos Santos

    Cisplatin has dramatically improved the survival rate of cancer patients, but it has also increased the prevalence of hearing and neurological deficits in this population. Cisplatin induces ototoxicity, peripheral (most prevalent) and central (rare) neurotoxicity. This review addresses the ototoxicity and the neurotoxicity associated with cisplatin-based chemotherapy, providing an integrated view of the potential protective agents that have been evaluated in vitro, in vivo and in clinical trials, their targets and mechanisms of protection and their effects on the antitumor activity of cisplatin. So far, the findings are insufficient to support the use of any oto- or neuroprotective agent before, during or after cisplatin chemotherapy. Despite their promising effects in vitro and in animal studies, many agents have not been evaluated in clinical trials. Additionally, the clinical trials have limitations concerning the sample size, controls, measurement, heterogeneous groups, several arms of treatment, short follow-up or no blinding. Besides that, for most agents, the effects on the antitumor activity of cisplatin have not been evaluated in tumor-bearing animals, which discourages clinical trials. Further well-designed randomized controlled clinical trials are necessary to definitely demonstrate the effectiveness of the oto- or neuroprotective agents proposed by animal and in vitro studies.

    更新日期:2019-12-29
  • Involvement of PERK-CHOP pathway in fumonisin B1- induced cytotoxicity in human gastric epithelial cells
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-28
    Song Yu; Bingxuan Jia; Yunxia Yang; Na Liu; Aibo Wu

    Fumonisin B1 (FB1) is a mycotoxin, produced by Fusarium verticillioides and Fusarium proliferatum, and a common fungal contaminant of maize worldwide. Its potential health hazard as a natural toxin is well documented in human and domestic animals. However, the molecular mechanism and the key factors responsible for FB1-induced cytotoxicity have not been elucidated. In this study, we first examined the cytotoxicity induced by FB1 in human gastric epithelial cell line (GES-1). We found that FB1 notably decreased cell viability and induced apoptotic cell death. Furthermore, the levels of ER stress markers were significantly increased after FB1 exposure and the ER stress inhibitor 4-phenylbutyric acid strongly suppressed FB1-induced cytotoxicity. Interestingly, the inhibition of PERK activity by GSK2606414 or shPERK3 blocked FB1-induced apoptotic cell death and cell proliferation suppression, which indicated that the cytotoxicity induced by FB1 was dependent on this signalling pathway. Moreover, myriocin could relieve FB1-induced ER stress and prevent cell death, which implied that the disruption of sphingolipid metabolism is an apical event for FB1-induced cytotoxicity. In the present study, we demonstrated that the ER stress-related PERK-CHOP signalling pathway is a novel mechanism for FB1-induced cytotoxicity and the gastrointestinal injury caused by FB1 should be concerned in the future.

    更新日期:2019-12-29
  • Egr1/p300/ACE signal mediates postnatal osteopenia in female rat offspring induced by prenatal ethanol exposure
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-28
    Zhixin Wu; Zhengqi Pan; Yinxian Wen; Hao Xiao; Yangfan Shangguan; Liaobin Chen; Hui Wang
    更新日期:2019-12-29
  • T-2 toxin-induced DRP-1-dependent mitophagy leads to the apoptosis of mice Leydig cells (TM3)
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-27
    Jing Wu; Jia-xin Chen; Jian-hua He

    T-2 toxin, one member of the type A trichothecene family, induces the apoptosis of human hepatocytes (L02) and murine Leydig cells (TM3), as well as mitochondrial dysfunctions. In the present study, we attempted to investigate whether T-2 toxin toxicity is related to mitochondrial dysfunction and mitophagy. We found that T-2 toxin might induce autophagy and mitophagy in TM3 cells (TM3) in a concentration-dependent manner. In addition, T-2 toxin could induce mitochondrial dysfunction, depolarization, and fission concentration-dependently. The inducible effects of T-2 toxin on mitophagy, mitochondrial dysfunction, and cell apoptosis could all be significantly reversed by autophagy inhibitor, 3 MA. Finally, DRP-1 participated in the inducible effects of T-2 toxin on TM3 cell mitophagy, mitochondrial dysfunction, and cell apoptosis. In summary, mitophagy and mitochondrial dysfunction are essential mechanisms of the toxicity induced by T-2 toxin. Thus, our findings provide a rationale for further studies on selectively targeting mitophagy to improve mitochondrial dysfunction and to protect cells from T-2 toxin-induced toxicity.

    更新日期:2019-12-27
  • Anxiolytic and antidepressant-like effects of Annona coriacea (Mart.) and caffeic acid in mice
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-27
    Álefe Brito Monteiro; Cristina Kelly de Souza Rodrigues; Emmily Petícia do Nascimento; Valterlúcio dos Santos Sales; Gyllyandeson de Araújo Delmondes; Maria Haiele Nogueira da Costa; Victor Afonso Pereira de Oliveira; Luis Pereira de Morais; Aline Augusti Boligon; Roseli Barbosa; José Galberto Martins da Costa; Irwin Rose Alencar de Menezes; Cícero Francisco Bezerra Felipe; Marta Regina Kerntopf

    This research evaluated the anxiolytic and antidepressant-like effects of a hydroethanolic extract from the leaves of Annona coriacea (EHFAC) and caffeic acid (CA). Mice were intraperitoneally treated with saline, EHFAC (1, 10, 20 mg/kg) or CA (0.15 mg/kg) and subject to the elevated plus-maze, open field, rota-rod, forced swimming and reserpine-induced akinesia tests. Pro-convulsant and anticholinergic effects were also evaluated. EHFAC presented anxiolytic-like effect on the elevated plus-maze, which was partially reversed by flumazenil. A similar effect was observed with CA. In the forced swimming test, EHFAC and CA reduced the immobility time of mice; such effect was potentiated when EHFAC or CA were associated with imipramine, bupropion and fluoxetine. The antidepressant-like effect was reinforced as EHFAC partially reversed the reserpine-induced akinesia. In addition, a pre-treatment with EHFAC and CA did not decrease the latency to 1st seizure of animals that received a sub-convulsive dose of PTZ, nor reduced the intensity of oxotremorine-induced tremors. Taken together, the results indicate that EHFAC and CA have anxiolytic and antidepressant-like effects, which involve important neurotransmitter systems, such as GABAergic and monoaminergic ones, being devoid of side effects, commonly associated with classical psychotropic drugs.

    更新日期:2019-12-27
  • The toxicity of the methylimidazolium ionic liquids, with a focus on M8OI and hepatic effects
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-27
    Alistair C. Leitch; Tarek M. Abdelghany; Philip M. Probert; Michael P. Dunn; Stephanie K. Meyer; Jeremy M. Palmer; Martin P. Cooke; Lynsay I. Blake; Katie Morse; Anna K. Rosenmai; Agneta Oskarsson; Lucy Bates; Rodrigo S. Figueiredo; Ibrahim Ibrahim; Colin Wilson; Noha F. Abdelkader; David E. Jones; Peter G. Blain; Matthew C. Wright

    Ionic liquids are a diverse range of charged chemicals with low volatility and often liquids at ambient temperatures. This characteristic has in part lead to them being considered environmentally-friendly replacements for existing volatile solvents. However, methylimidazolium ionic liquids are slow to break down in the environment and a recent study at Newcastle detected 1 octyl 3 methylimidazolium (M8OI) – an 8 carbon variant methylimidazolium ionic liquid - in soils in close proximity to a landfill site. The current M8OI toxicity database in cultured mammalian cells, in experimental animal studies and in model indicators of environmental impact are reviewed. Selected analytical data from the Newcastle study suggest the soils in close proximity to the landfill site, an urban soil lacking overt contamination, had variable levels of M8OI. The potential for M8OI - or a structurally related ionic liquid – to trigger primary biliary cholangitis (PBC), an autoimmune liver disease thought to be triggered by an unknown agent(s) in the environment, is reviewed.

    更新日期:2019-12-27
  • A multiple endpoint approach reveals potential in vitro anticancer properties of thymoquinone in human renal carcinoma cells
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-27
    J.G. Costa; V. Keser; C. Jackson; N. Saraiva; Íris Guerreiro; N. Almeida; S.P. Camões; R. Manguinhas; M. Castro; J.P. Miranda; A.S. Fernandes; N.G. Oliveira

    Thymoquinone (TQ) is a monoterpene isolated from the oil of Nigella sativa seeds. The aim of this work was to evaluate the cytotoxic effects induced by TQ and its impact on the migration and invasion potential of 786-O human renal cancer cells. These cells were exposed to TQ (1–100 μM) for 24 and 48 h and cell viability assessed using the Crystal Violet and MTS assays. TQ treatment clearly decreased cell viability in a concentration- and time-dependent manner. TQ exposure moderately increased intracellular ROS levels and co-incubation with reduced glutathione markedly increased cell viability. Moreover, the effect of TQ in the cell cycle distribution was evaluated using flow cytometry, and an increase in the sub-G1 population was observed, especially at 30 μM, along with an increase in the % of apoptotic cells. TQ did not show genotoxic effects at a non-cytotoxic concentration (1.0 μM). At this concentration level, TQ significantly decreased the collective migration of 786-O cells, whereas it had no effect in chemotactic migration. TQ also decreased the invasiveness potential of 786-O cells, as evaluated by the transwell invasion assay. Overall, these results suggest that TQ presents an anticancer potential in the context of renal cancer, warranting further investigation.

    更新日期:2019-12-27
  • 更新日期:2019-12-27
  • NDAT suppresses pro-inflammatory gene expression to enhance resveratrol-induced anti-proliferation in oral cancer cells
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-26
    Yih Ho; Chien-Yi Wu; Yu-Tang Chin; Zi-Lin Li; Yi-shin Pan; Tung-Yung Huang; Po-Yu Su; Sheng-Yang Lee; Dana R. Crawford; Kuan-Wei Su; Hsien-Chung Chiu; Ya-Jung Shih; Chun A. Changou; Yu-Chen S.H. Yang; Jaqulene Whang-Peng; Yi-Ru Chen; Hung-Yun Lin; Shaker A. Mousa; Kuan Wang

    Nano-diamino-tetrac (NDAT), a tetraiodothyroxine deaminated nano-particulated analog, has shown to inhibit expression of pro-inflammatory genes. NDAT inhibits expression of programmed death-ligand 1 (PD-L1). On the other hand, in addition to inhibiting inflammatory effect, the stilbene, resveratrol induces expression of cyclooxygenase-2 (COX-2) and its accumulation. Sequentially, inducible COX-2 complexes with p53 and induces p53-dependent anti-proliferation. In current study, we investigated mechanisms involved in combined treatment of NDAT and resveratrol on anti-proliferation in human oral cancer cells. Both resveratrol and NDAT inhibited expression of pro-inflammatory IL-1β and TNF-α. They also inhibited expression of CCND1 and PD-L1. Both resveratrol and NDAT induced BAD expression but only resveratrol induced COX-2 expression in both OEC-M1 and SCC-25 cells. Combined treatment attenuated gene expression significantly compared with resveratrol treatment in both cancer cell lines. Resveratrol reduced nuclear PD-L1 accumulation which was enhanced by a STAT3 inhibitor, S31-201 or NDAT suggesting that NDAT may inactivate STAT3 to inhibit PD-L1 accumulation. In the presence of T4, NDAT further enhanced resveratrol-induced anti-proliferation in both cancer cell lines. These findings provide a novel understanding of the inhibition of NDAT in thyroxine-induced pro-inflammatory effect on resveratrol-induced anticancer properties.

    更新日期:2019-12-27
  • Acyl moiety and temperature affects thermo-oxidative degradation of steryl esters. Cytotoxicity of the degradation products
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-26
    Maria Kasprzak; Magdalena Rudzińska; Dominik Kmiecik; Roman Przybylski; Anna Olejnik
    更新日期:2019-12-27
  • Immune Th17 lymphocytes play a critical role in the multiple beneficial properties of resveratrol
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-26
    Dominique Delmas; Emeric Limagne; François Ghiringhelli; Virginie Aires
    更新日期:2019-12-27
  • 更新日期:2019-12-27
  • Profiling the interaction of Al(III)-GFLX complex, a potential pollution risk, with bovine serum albumin
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-25
    Hua Chen; Chunlei Zhu; Feng Chen; Jingjing Xu; Xiuting Jiang; Zeyu Wu; Xiaowei Ding; Gao-Chao Fan; Yizhong Shen; Yingwang Ye

    Fluoroquinolone antibiotics (FQs), a new class of pollutants that seriously threaten human health through environmental and food residues, have aroused wide public concern. However, little attention has been paid to the potential toxicity of FQs' metal complex. Here, we firstly explore the proof-of-concept study of FQs' metal complex to bind bovine serum albumin (BSA) using systematical spectroscopic approaches. In detail, we have found that the complex of Al3+ with gatifloxacin (Al(III)-GFLX complex) can effectively bind to BSA via electrostatic interaction in PBS buffer (pH = 7.4, 1×), resulting in the formation of Al(III)-GFLX-BSA complex. The negative value of ΔG shows that the binding of Al(III)-GFLX complex to BSA is a spontaneous process. Circular dichroism spectra verify that Al(III)-GFLX complex effectively triggers the conformation changes of BSA's secondary structure. It has been proved that the interaction of small molecule with serum albumin has a significant effect on their in vivo biological effects such as absorption, distribution, metabolism, and excretion, and etc. Therefore, the results of this paper may offer a valuable theoretical basis for establishing safety standards of FQs' metal complex to ensure food and environmental health.

    更新日期:2019-12-25
  • 更新日期:2019-12-23
  • Role of autophagy in alcohol and drug-induced liver injury
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-23
    Jessica A. Williams; Wen-Xing Ding
    更新日期:2019-12-23
  • Terminalia bellirica extract induces anticancer activity through modulation of apoptosis and autophagy in oral squamous cell carcinoma
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-23
    Srimanta Patra; Prashanta Kumar Panda; Debasna Pritimanjari Panigrahi; Prakash Priyadarshi Praharaj; Chandra Sekhar Bhol; Kewal Kumar Mahapatra; Priyadarshini Padhi; Mrutyunjay Jena; Shankargouda Patil; Samir Kumar Patra; Sujit Kumar Bhutia
    更新日期:2019-12-23
  • Exploring the phytochemical profile of Cytinus hypocistis (L.) L. as a source of health-promoting biomolecules behind its in vitro bioactive and enzyme inhibitory properties
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-21
    Ana Rita Silva; José Pinela; Maria Inês Dias; Ricardo C. Calhelha; Maria José Alves; Andrei Mocan; Pablo A. García; Lillian Barros; Isabel C.F.R. Ferreira
    更新日期:2019-12-21
  • CYPs-mediated drug-drug interactions on psoralidin, isobavachalcone, neobavaisoflavone and daidzein in rats liver microsomes
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-21
    Mengjun Shi; Yiping Cui; Cunyu Liu; Changqin Li; Zhenhua Liu; Wen-yi Kang

    The incubation system of CYP2E1 and CYP3A4 enzymes in rat liver microsomes was established to investigate the effects of psoralidin, isobavachalcone, neobavaisoflavone and daidzein from Fructus Psoraleae in vitro. The relevant metabolites were measured by the method of high performance liquid chromatography (HPLC), after probe substrates of 4-nitrophenol, testosterone and the drugs at different concentrations were added to the incubation systems. In addition, real-time RT-PCR was performed to determine the effect of psoralidin, neobavaisoflavone and daidzein on the mRNA expression of CYP3A4 in rat liver. The results suggested that psoralidin, isobavachalcone and neobavaisoflavone were Medium-intensity inhibitors of CYP2E1 with Ki values of 2.58, 1.28 and 19.07 μM, respectively, which could inhibit the increase of CYP2E1 and reduce diseases caused by lipid peroxidation. Isobavachalcone (Ki = 37.52 μM) showed a weak competitive inhibition on CYP3A4. Psoralidin and neobavaisoflavone showed obvious induction effects on CYP3A4 in the expression level of mRNA, which could accelerate the effects of drug metabolism and lead to the risk of inducing DDIs and serious adverse reactions. The results could be used for guideline of Fructus Psoraleae in clinic, which aimed to calculate the drug toxicity by studying the drug-drug interactions caused by the induction and inhibition of CYP450.

    更新日期:2019-12-21
  • Hepatic injury and inflammation alter ethanol metabolism and drinking behavior
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-21
    Tianyi Ren; Bryan Mackowiak; Yuhong Lin; Yanhang Gao; Junqi Niu; Bin Gao

    While liver injury is commonly associated with excessive alcohol consumption, how liver injury affects alcohol metabolism and drinking preference remains unclear. To answer these questions, we measured the expression and activity of alcohol dehydrogenase 1 (ADH1) and acetaldehyde dehydrogenase 2 (ALDH2) enzymes, ethanol and acetaldehyde levels in vivo, and binge-like and preferential drinking behaviors with drinking in the dark and two-bottle choice in animal models with liver injury. Acute and chronic carbon tetrachloride (CCl4), and acute LPS-induced liver injury repressed hepatic ALDH2 activity and expression and consequently, blood and liver acetaldehyde concentrations were increased in these models. In addition, chronic CCl4 and acute LPS treatment inhibited hepatic ADH1 expression and activity, leading to increases in blood and liver ethanol concentrations. Consistent with the increase in acetaldehyde levels, alcohol drinking behaviors were reduced in mice with acute or chronic liver injury. Furthermore, oxidative stress induced by hydrogen peroxide attenuated ADH1 and ALDH2 activity post-transcriptionally, while proinflammatory cytokines led to transcriptional repression of ADH1 and ALDH2 in cultured hepatocytes, which correlated with the repression of transcription factor HNF4α. Collectively, our data suggest that alcohol metabolism is suppressed by inflammation and oxidative stress, which is correlated with decreased drinking behavior.

    更新日期:2019-12-21
  • GC-MS-FID characterization and antibacterial activity of the Mikania cordifolia essential oil and limonene against MDR strains
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-20
    Ana Carolina Justino de Araújo; Priscilla Ramos Freitas; Cristina Rodrigues dos Santos Barbosa; Débora Feitosa Muniz; Janaína Esmeraldo Rocha; Ana Cristina Albuquerque da Silva; Cícera Datiane de Morais Oliveira-Tintino; Jaime Ribeiro-Filho; Luiz Everson da Silva; Camila Confortin; Wanderlei do Amaral; Cícero Deschamps; José Maria Barbosa-Filho; Natanael Teles Ramos de Lima; Saulo Relison Tintino; Henrique Douglas Melo Coutinho

    The present study evaluated the effect of the essential oil of Mikania cordifolia (EOMc) and its major constituent limonene alone or associated with antibacterial drugs against Multidrug Resistant Bacteria (MDR). To evaluate the antibacterial activity, the minimum inhibitory concentrations (MIC) of the oil and limonene against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were determined. The antibiotic-modulating activity was assessed using subinhibitory concentrations (MIC/8) of these substances in combination with conventional antibacterial drugs. Although no relevant antibacterial activity of the natural products was detected, both substances modulated the action of antibiotics against resistant bacteria. The EOMc demonstrated the best modulating effect against P. aeruginosa, presenting synergistic effects when associated with gentamicin and norfloxacin. In addition, the oil reduced the MIC of norfloxacin against E. coli as well as reduced the MIC of gentamicin against S. aureus. On the other hand, the best effect of limonene was obtained against S. aureus. Thus, it is concluded that the essential oil Mikania cordifolia and the isolated compound limonene do not have clinically significant antibacterial effect, but modulate the action of antibiotics against MDR bacteria.

    更新日期:2019-12-20
  • Chemoprotective and antiobesity effects of tocols from seed oil of Maqui-berry: Their antioxidative and digestive enzyme inhibition potential
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-17
    José Miguel Bastías-Montes; Karen Monterrosa; Ociel Muñoz-Fariña; Olga García; Sergio M. Acuña-Nelson; Carla Vidal-San Martín; Roberto Quevedo-Leon; Isao Kubo; Jose G. Avila-Acevedo; Mariana Domiguez-Lopez; Zhao-Jun Wei; Kiran Thakur; Carlos L. Cespedes-Acuña

    Maqui-berry (Aristotelia chilensis) is the emerging Chilean superfruit with high nutraceutical value. Until now, the research on this commodity was focused on the formulations enriched with polyphenols from the pulp. Herein, contents of tocols were compared in the seed oil of Maqui-berry obtained through three different extraction methods followed by determining their antioxidative and enzyme inhibitions in-vitro. Firstly, oilseed was extracted with n-hexane (Soxhlet method), chloroform/methanol/water (Bligh and Dyer method) and pressing (industrial). These samples were used to access their effects against DPPH, HORAC, ORAC, FRAP, Lipid-peroxidation (TBARS), α-amylase, α-glucosidase, and pancreatic lipase. All the isomers of tocopherol and tocotrienol were identified, and β-sitosterol was the only sterol found in higher amounts than other vegetable oils. The Bligh and Dyer method could lead to the highest antioxidative capacity compared to Soxhlet and press methods likely because the latter have a higher amount of tocopherols. Further, seed oil from Maqui berry and their tocols (α, β, γ, δ-tocopherols, tocotrienols, and β-sitosterol) warrant clinical investigation for their antioxidative and antiobesity potential. Taken together, these findings provide relevant and suitable conditions for the industrial processing of Maqui-berry.

    更新日期:2019-12-18
  • Antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil in mice
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-17
    Renata de Souza Sampaio; Emmily Petícia do Nascimento; Irwin Rose Alencar de Menezes; Valterlúcio dos Santos Sales; Anita Oliveira Brito Pereira; Giovana Mendes de Lacerda; Enaide Soares Santos; Maria Janice Pereira Lopes; Luanna Gomes da Silva; Gyllyandeson de Araújo Delmondes; Nélio Barreto Vieira; Victor Mantoani Zaia; Daniel Souza Bezerra; José Galberto Martins da Costa; Cícero Francisco Bezerra Felipe; Marta Regina Kerntopf

    Chronic pain management has several adverse effects and research looking for new and effective pain management drugs posing lower undesirable effects is necessary. Given the above, the pharmacological investigation of medicinal plants significantly contributes to the dissemination of plant-derived therapeutics. The aim of this study was to evaluate the antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil (PBEO) and the participation of the opioid pathway in this effect in mice. Swiss Mus musculus male mice were tested using acute nociception models (acetic acid induced abdominal contortions, formalin, capsaicin and hot plate tests). The possible myorelaxant action of the PBEO was tested using the rotarod test. The essential oil reduced animal nociception in chemical and heat models, with this action being devoid of a myorelaxant effect. Naloxone (2 mg/kg, intraperitoneally – i.p.) partially antagonized the PBEO activity, possibly acting via opioid receptors. The results obtained provide evidence that the traditional Psidium brownianum use may be effective for pain treatment.

    更新日期:2019-12-18
  • Radioprotection of EGCG based on immunoregulatory effect and antioxidant activity against 60Coγ radiation-induced injury in mice
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-16
    Juanjuan Yi; Chen Chen; Xin Liu; Qiaozhen Kang; Limin Hao; Jinyong Huang; Jike Lu
    更新日期:2019-12-17
  • Utilisation of Rhododendron luteum Sweet bioactive compounds as valuable source of enzymes inhibitors, antioxidant, and anticancer agents
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-16
    Mohamad Fawzi Mahomoodally; Elwira Sieniawska; Kouadio Ibrahime Sinan; Marie Carene Nancy Picot-Allain; Serife Yerlikaya; Mehmet Cengiz Baloglu; Yasemin Celik Altunoglu; Ismail Senkardes; Kannan RR. Rengasamy; Gokhan Zengin

    Ethnobotanical evidences report the use of Rhododendron luteum Sweet (Ericaceae) in traditional medicinal systems. However, R. luteum has been associated to the occurrence of ‘mad honey’ poisoning. In the present study, the ethyl acetate, methanol, and water extracts of R. luteum were investigated for their in vitro antioxidant, enzyme inhibition, and cytotoxic properties. The cytotoxicity of R. luteum extracts on A549 lung cancer cell line was evaluated using MTT cell viability assay. Besides, HPLC-ESI-MSn approach was employed to elucidate the secondary metabolite profiles of R. luteum in order to establish any structure-activity relationship. Methanol and water extracts of R. luteum possessed highest radical scavenging and reducing properties while the ethyl acetate extract showed highest metal chelating properties. In terms of enzyme inhibition, the methanol and ethyl acetate extracts of R. luteum, possessing epigallocatechin, were active inhibitors of cholinesterase enzymes, α-glucosidase, and tyrosinase. Water extract caused growth inhibition of A549 cells with 207.2 μg/ml IC50 value. Though R. luteum has received little scientific attention due to the occurrence of grayanotoxins in the plant, however, data presented in this work shows promising biological activity of R. luteum and highlighted its role as a potential source of antioxidant and key enzyme inhibitors.

    更新日期:2019-12-17
  • Extraction and characterization of phenolic compounds with antioxidant and antimicrobial activities from pickled radish
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-14
    Jian Li; Shi-Ying Huang; Qianying Deng; Guiling Li; Guocheng Su; Jingwen Liu; Hui-Min David Wang
    更新日期:2019-12-17
  • Reduced testicular steroidogenesis in rat offspring by prenatal nicotine exposure: Epigenetic programming and heritability via nAChR/HDAC4
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-14
    Qi Zhang; Lin-guo Pei; Min Liu; Feng Lv; Guanghui Chen; Hui Wang

    Prenatal nicotine exposure (PNE) may lead to offspring's testicular dysplasia. Here, we confirmed the intergenerational effect of PNE on testosterone synthetic function and explored its epigenetic programming mechanism. Pregnant Wistar rats were injected subcutaneously with nicotine (2 mg/kg.d) from gestational day 9–20. Some dams were anesthetized to obtain fetal rats, the rest were allowed to spontaneous labor to generate F1 and F2 generation. In utero, PNE impaired testicular development and testosterone production. Meanwhile, the expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were decreased both in F1 and F2 generations. Furthermore, PNE enhanced the expression of fetal testicular nicotinic acetylcholine receptors (nAChRs) and histone deacetylase 4 (HDAC4), while obviously weakened histone 3 lysine 9 acetylation (H3K9ac) level of StAR/3β-HSD promoter from GD20 to postnatal week 12 and even in F2 generation. In vitro, nicotine increased nAChRs and HDAC4 expression, and decreased the StAR/3β-HSD H3K9ac level and expression, as well as the testosterone production in Leydig cells. Antagonism of nAChRs and inhibition of HDAC4 reversed the aforementioned changes. In conclusion, PNE programmed testicular low steroidogenesis and its heritability in male offspring rats. The underlying mechanism was associated to the low-level programming of StAR/3β-HSD H3K9ac via nAChR/HDAC4.

    更新日期:2019-12-17
  • 更新日期:2019-12-17
  • Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-12
    Patrick Wellington da Silva dos Santos; Ana Rita Thomazela Machado; Rone Aparecido De Grandis; Diego Luis Ribeiro; Katiuska Tuttis; Marco Morselli; Alexandre Ferro Aissa; Matteo Pellegrini; Lusânia Maria Greggi Antunes

    Abnormal epigenetic alterations are one of the keystones of cancer development. Epigenetic targeting drugs have become a promising and effective cancer therapy strategy. However, due to the high toxicity and unclear mechanisms of action of these drugs, natural compounds that cause epigenetic modulation have also been studied. Sulforaphane (SFN) is a promising bioactive compound for epigenetic targeting therapy. In this study, we investigate the effects of SFN on gene expression and DNA methylation in human hepatocellular carcinoma cells (HepG2). Using high throughput technologies in combination with cell-based assays, we find SFN is a potent anticancer agent, as it induces DNA damage, mitotic spindle abnormalities followed by apoptosis and proliferation inhibition in HepG2 cells. Our results show the upregulation of DNA damage response and cell cycle checkpoint genes. Also, we find the downregulation of pathways frequently overexpressed in human cancer. As expected, SFN exerts epigenetic modulation effects by inhibiting histone deacetylases (HDACs). SFN might affect the activity of oncogenic TF through methylation of its binding sites motifs. Our findings offer insights into SFN chemopreventive molecular effects in HepG2 cells and highlight SFN as a valuable natural approach to cancer therapy for future investigation.

    更新日期:2019-12-13
  • Camel milk rescues neurotoxic impairments induced by fenpropathrin via regulating oxidative stress, apoptotic, and inflammatory events in the brain of rats
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-12
    Yasmina M. Abd-Elhakim; Nabela I. El-Sharkawy; Hesham H. Mohammed; Lamiaa L.M. Ebraheim; Mostafa A. Shalaby

    This study explored the camel milk (CM) efficacy to ameliorate the fenpropathrin (FNP) induced neurotoxic impacts in rats. Six groups were orally administered physiological saline, corn oil, CM (2ml/rat/day), FNP (15 mg/kg bw daily for 60 days), CM/FNP (protective) or FNP + CM (therapeutic). Sensorimotor functions, memory, exploratory, and locomotor activities were assessed. The levels of dopamine (DOPA) neurotransmitter, acetylcholinesterase (AChE) enzyme, oxidative stress, and inflammatory markers were determined. Brain histopathology and apoptotic markers immunohistochemical detection were performed. The results revealed that FNP exposure resulted in deficit sensorimotor functions, impaired memory, and less exploration. DOPA and AChE Levels were significantly reduced. FNP exposure increased nitric oxide, malondialdehyde, myeloperoxidase, caspase-3, and tumor necrosis factor-alpha levels but interleukin 10, total antioxidant capacity, and Bcl-2 levels were declined. Also, FNP exposure induced obvious encephalopathy. Additionally, neurodegenerative changes were seen in the hippocampi of FNP-treated rats. FNP Exposure induced a significant decrease of Bcl-2 immunolabelling but Caspase-3 immunoexpression was increased in cerebral cortices and hippocampus tissues. CM significantly counteracted the FNP injurious impacts, especially when used as a prophylactic routine than a therapeutic one. Conclusively, these findings confirmed that CM could be a biologically effective protective agent against FNP induced neurobehavioral aberrations and neurotoxic impacts.

    更新日期:2019-12-13
  • Anti-fatigue effect of aqueous extract of Hechong (Tylorrhynchus heterochaetus) via AMPK linked pathway
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-10
    Ziqing Yang, Christudas Sunil, Muthukumaran Jayachandran, Xuchu Zheng, Kuopeng Cui, Yuepeng Su, Baojun Xu
    更新日期:2019-12-11
  • In-vitro degradation and toxicological assessment of pulsed electric fields crosslinked zein-chitosan-poly(vinyl alcohol) biopolymeric films
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-10
    Stephen G. Giteru, Belinda Cridge, Indrawati Oey, Azam Ali, Eric Altermann
    更新日期:2019-12-11
  • Developmental exposure to diacetoxyscirpenol reversibly disrupts hippocampal neurogenesis by inducing oxidative cellular injury and suppressed differentiation of granule cell lineages in mice
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-10
    Kota Nakajima, Yuko Ito, Satomi Kikuchi, Hiromu Okano, Kazumi Takashima, Gye-Hyeong Woo, Toshinori Yoshida, Tomoya Yoshinari, Yoshiko Sugita-Konishi, Makoto Shibutani

    To investigate the developmental exposure effect of diacetoxyscirpenol (DAS) on postnatal hippocampal neurogenesis, pregnant ICR mice were provided a diet containing DAS at 0, 0.6, 2.0, or 6.0 ppm from gestational day 6 to day 21 on weaning after delivery. Offspring were maintained through postnatal day (PND) 77 without DAS exposure. On PND 21, neural stem cells (NSCs) and all subpopulations of proliferating progenitor cells were suggested to decrease in number in the subgranular zone (SGZ) at ≥ 2.0 ppm. At 6.0 ppm, increases of SGZ cells showing TUNEL+, metallothionein-I/II+, γ-H2AX+ or malondialdehyde+, and transcript downregulation of Ogg1, Parp1 and Kit without changing the level of double-stranded DNA break-related genes were observed in the dentate gyrus. This suggested induction of oxidative DNA damage of NSCs and early-stage progenitor cells, which led to their apoptosis. Cdkn2a, Rb1 and Trp53 downregulated transcripts, which suggested an increased vulnerability to DNA damage. Hilar PVALB+ GABAergic interneurons decreased and Grin2a and Chrna7 were downregulated, which suggested suppression of type-2-progenitor cell differentiation. On PND 77, hilar RELN+ interneurons increased at ≥ 2.0 ppm; at 6.0 ppm, RELN-related Itsn1 transcripts were upregulated and ARC+ granule cells decreased. Increased RELN signals may ameliorate the response to the decreases of NSCs and ARC-mediated synaptic plasticity. These results suggest that DAS reversibly disrupts hippocampal neurogenesis by inducing oxidative cellular injury and suppressed differentiation of granule cell lineages. The no-observed-adverse-effect level of DAS for offspring neurogenesis was determined to be 0.6 ppm (0.09–0.29 mg/kg body weight/day).

    更新日期:2019-12-11
  • 更新日期:2019-12-11
  • Hemistepsin A alleviates liver fibrosis by inducing apoptosis of activated hepatic stellate cells via inhibition of nuclear factor-κB and Akt
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-09
    Jae Kwang Kim, Nu Ri Han, Sang Mi Park, Kyung Hwan Jegal, Ji Yun Jung, Eun Hye Jung, Eun Ok Kim, Doyeon Kim, Dae Hwa Jung, Jong Rok Lee, Chung A. Park, Sae Kwang Ku, Ilje Cho, Sang Chan Kim

    Hemistepsin A (HsA), isolated from Hemistepta lyrata (Bunge) Bunge, has the ability to ameliorate hepatitis in mice. However, the effects of H. lyrata and HsA on other types of liver disease have not been explored. In this report, we investigated the effects of H. lyrata and HsA on liver fibrosis and the underlying molecular mechanisms in activated hepatic stellate cells (HSCs). Based on cell viability-guided isolation, we found HsA was the major natural product responsible for H. lyrata-mediated cytotoxicity in LX-2 cells. HsA significantly decreased the viability of LX-2 cells and primary activated HSCs, increased the binding of Annexin V, and altered the expression of apoptosis-related proteins, suggesting that HsA induces apoptosis in activated HSCs. HsA reduced the phosphorylation of IKKε and the transactivation of nuclear factor-κB (NF-κB). Moreover, HsA decreased the phosphorylation of Akt and its downstream signaling molecules. Transfection experiments suggested that inhibition of NF-κB or Akt is essential for HsA-induced apoptosis of HSCs. In a CCl4-induced liver fibrosis model, HsA administration significantly decreased ALT and AST activities. Furthermore, HsA attenuated CCl4-mediated collagen deposits and profibrogenic genes expression in hepatic tissue. Thus, HsA may serve as a natural product for managing liver fibrosis through inhibition of NF-κB/Akt-dependent signaling.

    更新日期:2019-12-11
  • Sildenafil and tadalafil reduce the risk of contrast-induced nephropathy by modulating the oxidant/antioxidant balance in a murine model
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-09
    Andrei Mihai Iordache, Anca Oana Docea, Ana Maria Buga, Ovidiu Zlatian, Marius Eugen Ciurea, Otilia Constantina Rogoveanu, Florin Burada, Simona Sosoi, Radu Mitrut, Charalampos Mamoulakis, Dana Albulescu, Ramona Constantina Vasile, Aristides Tsatsakis, Daniela Calina
    更新日期:2019-12-09
  • Outstanding insecticidal activity and sublethal effects of Carlina acaulis root essential oil on the housefly, Musca domestica, with insights on its toxicity on human cells
    Food Chem. Toxicol. (IF 3.775) Pub Date : 2019-12-07
    Roman Pavela, Filippo Maggi, Riccardo Petrelli, Loredana Cappellacci, Michela Buccioni, Alessandro Palmieri, Angelo Canale, Giovanni Benelli
    更新日期:2019-12-07
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