Food and Chemical Toxicology

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ISSN / EISSN : 0278-6915 / 1873-6351
Published by: Elsevier BV (10.1016)
Total articles ≅ 14,752
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Canrui Yang, , Yixiang Cui, Guanghai Yu, Yinchen Hou, Long Pan, Wenjing Chen, Shuainan Zheng, Xiaoxiao Li, Jiarui Ma, et al.
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112240

Abstract:
Wheat Embryo Globulin (WEG) is a high-quality plant-derived protein with anti-inflammatory, antioxidant, and immunity enhancement effects. WEG was prepared and characterized using free amino acid analysis, circular dichroism (CD), and scanning electron microscope (SEM). The liver protection effect of WEG on mice after acute alcohol stimulation was also investigated. Male KM mice were randomly divided into four groups (n = 10). Animals were orally administrated with WEG (60 mg/kg), silymarin (50 mg/kg), and the same volume of saline solution daily for 30 days, before administering an alcohol-intragastric injection. Results displayed that the liver index, the levels of serum total cholesterol (TC), serum triglyceride (TG), liver malondialdehyde (MDA) and the mRNA expression of CYP2E1were significantly decreased in WEG-treated mice compared with the model group. Meanwhile, the levels of serum high-density lipoprotein-cholesterol (HDL-C), hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and the mRNA expression of ADH2 and ALDH2 were remarkably increased. Effect of WEG on histopathology of liver tissue confirmed its protective function. Meanwhile, GSH level of ileal was significantly increased, MDA was remarkably decreased in WEG-treated mice, which also indicated that WEG possessed a positive effect on intestinal micro ecological environment health to some extent. In conclusion, WEG is a promising agent for the prevention of acute alcoholic liver injury.
, Merve Ercin, Serap Sancar, Ertan Celik, Meral Koyuturk, Sema Bolkent, Sehnaz Bolkent
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112264

Abstract:
This study aimed to investigate the molecular effects of the common natural sugar glucose and artificial sweetener aspartame on cancer stem cell (CSC) population and cancer aggressiveness of PANC-1 human pancreas adenocarcinoma cells. According to our findings while aspartame exposure significantly increased the CSC population, high glucose had no effect on it. The epithelial-mesenchymal transition marker N-cadherin increased only in the aspartame group. The findings indicate that a high level of glucose exposure does not effect the invasion and migration of PANC-1 cells, while aspartame increases both of these aggressiveness criteria. The findings also suggest that a high concentration of glucose maintains CSC population through induction of nuclear Oct3/4 and differentiation to parental cells via increasing cytoplasmic c-myc. Aspartame exposure to PANC-1 cells activated AKT and deactivated GSK3β by increasing levels of ROS and cytoplasmic Ca+2, respectively, through T1R2/T1R3 stimulation. Then p-GSK3β(Ser9) boosted the CSC population by increasing pluripotency factors Oct3/4 and c-myc via NICD, GLI1 and p21. In the aspartame group, T1R1 silencing further increased the CSC population but decreased cell viability and suppressed the p21, NICD and GLI activation. The presence and amount of T1R subunits in the membrane fraction of PANC-1 cells are demonstrated for the first time in this study, as is the regulatory effect of T1R1's on CSC population. In conclusion, the present study demonstrated that long-term aspartame exposure increases CSC population and tumor cell aggressiveness through p21, NICD, GLI1. Moreover, while aspartame had no tumorigenic effect, it could potentially advance an existing tumor.
Elizabeth Undiano, Susana Chávez, Pedro Mederos, ,
Published: 1 July 2021
Food and Chemical Toxicology; doi:10.1016/j.fct.2021.112408

Abstract:
Acute toxicity of organophosphate (OPs) pesticides is a public health problem. The adverse effects are associated with the inhibition and aging of nervous system B-esterases such as acetyl cholinesterase (AChE) and neuropathic target esterase (NTE). Treatment based on A-esterases such as mammal serum paraoxonase-1 has been suggested. This ex vivo study shows the Cu2+-dependent hydrolysis of trichloronat (TCN), a racemic organophosphonothioate insecticide, in human and domestic mammal serum (dog, goat, pig, sheep and cow). Ca2+-dependent (2.5 mM) or EDTA-resistant (5 mM) activity (1–6%) was not significant (p ˃ 0.05) in all samples, except goat serum and its albumin, which showed higher levels of TCN hydrolysis (38–58%) than other mammals with 100 and 300 μM copper sulfate at physiological conditions for 60 min. Goat serum albumin (GSA) showed significant (p˂0.05) stereoselective hydrolysis (+)-TCN ˃ (−)-TCN (45% versus 33%). This suggests that GSA is the protein responsible for Cu2+-dependent TCNase activity in goat serum. This is the first report on Cu2+-dependent A-esterase activity in mammalian tissues. This goat serum cuproprotein could be considered as an alternative in future biotechnological applications including enantiomeric synthesis, bioremediation and antidotal treatment of organophosphonothioate pesticide poisoning.
Xuyao Li, , Manki Ho, Allyson Marshall-Hudson, Rebecca Gross, Michael E. Casser,
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112277

Abstract:
Streptococcus salivarius DB-B5 was previously isolated from the supragingival plaque of a healthy female adult and selected for development as a probiotic candidate for oral health. Probiotics are an important emerging therapeutic method for preventing, treating, and maintaining oral health. Although S. salivarius is a predominant member of the commensal oral microbiota and generally regarded as a safe species, it is recognized that each strain needs to be comprehensively assessed for safety. This study describes the in silico, in vitro, and clinical testing that were conducted to evaluate the safety of S. salivarius DB-B5. Both 16S rRNA and multi-gene phylogenetic reconstruction was used to confirm the taxonomic identity of this strain. Bioinformatic analysis of the genome demonstrated the absence of transmissible antibiotic resistance genes or virulence factors. Phenotypic testing further showed S. salivarius DB-B5 to be susceptible to clinically relevant antibiotics. S. salivarius DB-B5 displayed weak alpha-hemolysis, and does not produce biogenic amines. In a randomized, double-blind, placebo-controlled clinical study, consumption of S. salivarius DB-B5 at 10 billion CFU/day for 4 weeks by healthy adults was safe and well-tolerated (ClinicalTrials.gov registry number NCT04492631). This work has indicated that S. salivarius DB-B5 is a safe probiotic candidate.
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112228

Abstract:
Caffeine use in the population is widespread. Caffeine withdrawal in the hospital setting is an underappreciated syndrome with symptoms including drowsiness, difficulty concentrating, mood disturbances, low motivation, flu-like symptoms, and headache. Withdrawal may occur upon abstinence from chronic daily exposure at doses as low as 100 mg/day and following only 3–7 days of consumption at higher doses. There are limited data investigating how caffeine withdrawal contributes to hospital morbidity. Some studies suggest caffeine withdrawal may contribute to intensive care delirium and that caffeine may promote wakefulness post-anesthesia. Caffeine supplementation has also shown promise in patients at risk of caffeine withdrawal, such as those placed on nil per os (NPO) status, in preventing caffeine withdrawal headache. These data on caffeine supplementation are not entirely consistent, and routine caffeine administration has not been implemented into clinical practice for patients at risk of withdrawal. Notably, caffeine serves a therapeutic role in the hospital for other conditions. Our review demonstrates that caffeine is largely safe in the general population and may be an appropriate therapeutic option for future studies, if administered properly. There is a need for a randomized controlled trial investigating in-hospital caffeine supplementation and the population that this would best serve.
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112290

Abstract:
One of the most widely used flavour enhancers in the food industry is monosodium glutamate (MSG). MSG consumption has been on an upward trend, worrying in terms of potential toxic effects. This review is focused on the long-term toxicity of MSG and the experimental evidence that supports it. The article's primary purpose was to survey recently published data regarding the consumption of MSG within safe limits. The administered doses in animal models are very varied and have given rise to controversy. Also, the paper comprises pathways to lower MSG toxicity and highlight other underexploited biological effects, as anti-cancer potential. The administration of MSG, combined with various compounds, has been shown benefit against toxic effects. Several recent studies have identified a possible mechanism that recommends MSG and some derivatives as potential anti-cancer agents. New anti-cancer compounds based on the glutamic acid structure must be studied and further exploited. International regulations require harmonization of safe doses of MSG based on current scientific studies. Replacing MSG with other umami flavour enhancers may be a safer alternative for human health in the future. The biological consequences of MSG consumption or therapeutical administration have not been fully deciphered yet.
, Jiajia Su, Die Wu, Leran Wang, Jiangning Hu, ,
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112289

Abstract:
Fritillaria thunbergii Miq. (Zhe beimu) ranked as oldest known homeopathic traditional folk medicine in China. The bulbs are medicinally important curing cough, inflammation, gastric ulcers, hypertension, diarrhea, and bronchitis. The aim of this review is to enlighten the deeper knowledge about F. thunbergii giving a comprehensive overview on its traditional uses, phytochemistry and pharmacology for future investigation of plant-based drugs and therapeutic applications. Total 48 medicinally important species of Fritillaria were described; total 122 compounds have been identified as results only 72 chemical constituents were described with proper chemical and biological details. F. thunbergii and its bulbs mainly constitute alkaloids, essential oils, diterpenoids, carbohydrates, sterols, amino acids, nucleosides, fatty acids, and lignans. The pharmacological studies demonstrate that F. thunbergii and its bulbs displays a wide range of bioactivities e.g., anti-inflammatory, anticancer, antitussive, expectorant, anti-ulcer, antimicrobial, antioxidant, anti-thyroid, regulation of blood rheology, anti-diarrhea, neuroprotection, and analgesic effects. Although promising reports on the various chemical bioactive constituents and biological properties of F. thunbergii have been published, very few reviews are related specifically to the traditional uses, phytochemistry and pharmacological applications. Further, various other studies on these plants should deserve our more attention for future investigation for drug development and its therapeutic applications.
, Pauline Rebouillat, Benjamin Allès, Jean-Pierre Cravedi, , Serge Hercberg, Denis Lairon, Rodolphe Vidal, Emmanuelle Kesse-Guyot
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112179

Abstract:
To examine dietary exposure to 25 pesticide residues in several diet groups including omnivores, pesco-vegetarians, vegetarians and vegans while accounting for the farming system (organic or conventional) of plant-based foods consumed. Organic and conventional consumption data in combination with data on pesticide residues in plant-based foods were used to derive estimated dietary exposure to pesticide residues. Pesticide residue exposure was estimated based on observed data, and using two scenarios simulated for 100%-conventional and 100%-organic diets in 33,018 omnivores, 555 pesco-vegetarians, 501 vegetarians and 368 vegans from the NutriNet-Santé study. Pesticide residue exposure across groups was compared using Kruskal-Wallis tests. Exposure levels varied across diet groups depending on the pesticide studied. The highest exposure was observed for imazalil in all groups. Vegetarians appeared to be less exposed to the studied pesticides overall. Compared to omnivores – apart from pesticides authorised in organic farming – vegetarians had lowest exposure. The 100%-conventional scenario led to a sharp increase in exposure to pesticide residues, except for pesticides allowed in organic farming and conversely for the 100%-organic scenario. Despite their high plant-based product consumption, vegetarians were less exposed to synthetic pesticides than omnivores, due to their greater propensity to consume organic.
Letícia A. Apolinário, Leandra N.Z. Ramalho, Motahareh Hashemi Moosavi, Alessandra V. Jager, Marlei J. Augusto, Maurício R. Trotta, Tânia Petta, , , Fernando S. Ramalho
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112263

Abstract:
In this study, the changes in oncogenic and tumor suppressor signaling pathways in liver and their association with serum and urinary biomarkers of aflatoxin exposure were evaluated in Wistar rats fed diets containing aflatoxin B1 (AFB1) for 90 days. Rats were divided into four groups (n = 15 per group) and assigned to dietary treatments containing 0 (control), 50 (AFB50), 100 (AFB100) and 200 μg AFB1 kg−1 diet (AFB200). Multiple preneoplastic foci of hepatocytes marked with glutathione-S-transferase-placental form (GST-P) were identified in AFB100 and AFB200 groups. Hepatocellular damage induced by AFB1 resulted in overexpression of cyclin D1 and β-catenin. The liver expression of retinoblastoma (Rb) and p27Kip1 decreased in AFB100 and AFB200 groups, confirming the favorable conditions for neoplastic progression to hepatocellular carcinoma. All samples from rats fed AFB1-contaminated diets had quantifiable AFB1-lysine in serum or urinary AFM1 and AFB1-N7-guanine, with mean levels of 20.42–50.34 ng mL−1, 5.31–37.68 and 39.15–126.37 ng mg−1 creatinine, respectively. Positive correlations were found between AFB1-lysine, AFM1 or AFB1-N7-guanine and GST-P+, β-catenin+ and cyclin D1+ hepatocytes, while Rb + cells negatively correlated with those AFB1 exposure biomarkers. The pathways evaluated are critical molecular mechanisms of AFB1-induced hepatocarcinogenesis in rats.
M. Alonso-Garrido, M. Frangiamone, G. Font, , L. Manyes
Published: 1 July 2021
Food and Chemical Toxicology, Volume 153; doi:10.1016/j.fct.2021.112261

Abstract:
Food and feed are daily exposed to mycotoxin contamination which effects may be counteracted by antioxidants like carotenoids. Some mycotoxins as well as carotenoids penetrate the blood brain barrier (BBB) inducing alterations related to redox balance in the mitochondria. Therefore, the in vitro BBB model ECV304 was subcultured for 7 days and exposed to beauvericine, enniatins, ochratoxin A, zearalenone (100 nM each), individually and combined, and pumpkin extract (500 nM). Reactive oxygen species were measured by fluorescence using the dichlorofluorescein diacetate probe at 0 h, 2 h and 4 h. Intracellular ROS generation reported was condition dependent. RNA extraction was performed and gene expression was analyzed by qPCR after 2 h exposure. The selected genes were related to the Electron Transport Chain (ETC) and mitochondrial activity. Gene expression reported upregulation for exposures including mycotoxins plus pumpkin extract versus individual mycotoxins. Beauvericin and Beauvericin-Enniatins exposure significantly downregulated Complex I and pumpkin addition reverted the effect upregulating Complex I. Complex IV was the most downregulated structure of the ETC. Thioredoxin Interacting Protein was the most upregulated gene. These data confirm that mitochondrial processes in the BBB could be compromised by mycotoxin exposure and damage could be modulated by dietary antioxidants like carotenoids.
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