Nonalcoholic Fatty Liver Disease Is a Susceptibility Factor for Perchloroethylene-Induced Liver Effects in Mice
| العنوان: | Nonalcoholic Fatty Liver Disease Is a Susceptibility Factor for Perchloroethylene-Induced Liver Effects in Mice |
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| المؤلفون: | David W. Threadgill, Igor P. Pogribny, Joseph A. Cichocki, Weihsueh A. Chiu, Yasuhiro Iwata, Kranti Konganti, Shinji Furuya, Ivan Rusyn, Yu-Syuan Luo |
| المصدر: | Toxicological Sciences. 159:102-113 |
| بيانات النشر: | Oxford University Press (OUP), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Tetrachloroethylene, Real-Time Polymerase Chain Reaction, Toxicology, Gas Chromatography-Mass Spectrometry, Nfald and Perchloroethylene-Induced Liver Injury, chemistry.chemical_compound, Mice, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Animals, Liver X receptor, Carcinogen, business.industry, Reverse Transcriptase Polymerase Chain Reaction, nutritional and metabolic diseases, medicine.disease, Corrigenda, digestive system diseases, Mice, Inbred C57BL, Endocrinology, 030104 developmental biology, chemistry, 030211 gastroenterology & hepatology, Liver function, Disease Susceptibility, Steatosis, Steatohepatitis, Chemical and Drug Induced Liver Injury, Xenobiotic, business, Transcriptome, Drug metabolism, Chromatography, Liquid |
| الوصف: | Nonalcoholic fatty liver disease (NAFLD) is the most prevalent pathological liver condition in developed countries. NAFLD results in severe alterations in liver function, including xenobiotic metabolism. Perchloroethylene (PERC) is a ubiquitous environmental pollutant, a known hepatotoxicant in rodents, and a probable human carcinogen. It is known that PERC disposition and metabolism are affected by NAFLD in mice; here, we examined how NAFLD changes PERC-associated liver effects. Male C57Bl6/J mice were fed a low-fat diet (LFD), high-fat diet (HFD), or methionine/folate/choline-deficient diet (MCD) to model a healthy liver, or mild and severe forms of NAFLD, respectively. After 8 weeks on diets, mice were orally administered PERC (300 mg/kg/day) or vehicle (5% aqueous Alkamuls-EL620) for 5 days. PERC-induced liver effects were exacerbated in both NAFLD groups. PERC exposure was associated with up-regulation of genes involved in xenobiotic, lipid, and glutathione metabolism, and down-regulation of the complement and coagulation cascades, regardless of the diet. Interestingly, HFD-fed mice, not MCD-fed mice, were generally more sensitive to PERC-induced liver effects. This was indicated by histopathology and transcriptional responses, where induction of genes associated with cell cycle and inflammation were prominent. Liver effects positively correlated with diet-specific differences in liver concentrations of PERC. We conclude that NAFLD alters the toxicodynamics of PERC and that NAFLD is a susceptibility factor that should be considered in future risk management decisions for PERC and other chlorinated solvents. |
| تدمد: | 1096-0929 1096-6080 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4354fbab93b11fbe24924fade414189 https://doi.org/10.1093/toxsci/kfx120 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a4354fbab93b11fbe24924fade414189 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10960929 10966080 |
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