Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk (Korea, Republic of)
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of)
- Huons Research Center, Gyonggido (Korea, Republic of)
- Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of)
Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [{sup 14}C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.
- OSTI ID:
- 22687879
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 291; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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