Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice
| Autor: | Gavin E. Arteel, Robin H. Schmidt, Hai Zhong, Juliane I. Beier, Min Tan, J. Christopher States, Walter H. Watson |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Sodium arsenite Arsenites chemistry.chemical_element Weight Gain Toxicology Article Mice chemistry.chemical_compound Liver Function Tests Non-alcoholic Fatty Liver Disease Risk Factors Internal medicine medicine Animals Arsenic Inflammation Pharmacology Fibrin medicine.diagnostic_test Fatty liver food and beverages medicine.disease Dietary Fats Sodium Compounds Extracellular Matrix Fatty Liver Mice Inbred C57BL Disease Models Animal Endocrinology chemistry Toxicity Chemical and Drug Induced Liver Injury medicine.symptom Metabolic syndrome Steatohepatitis Liver function tests Weight gain |
| Zdroj: | Toxicology and Applied Pharmacology. 257:356-364 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2011.09.019 |
| Popis: | Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. |
| Databáze: | OpenAIRE |
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