title: Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity.
abstract: 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 [(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.
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, South Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Won
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, South Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Song
authors.affiliation: Huons Research Center, Gyonggido, South Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine, Daejeon, South Korea.
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, South Korea.
authors.forename: Og-Sung
authors.initials: OS
authors.lastname: Moon
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, South Korea.
authors.forename: Hyoung-Chin
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, South Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Son
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, South Korea. Electronic address: hyojung@cnu.ac.kr.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D013853:Thioacetamide / Q000378:metabolism / Q000633:toxicity*
chemical_list: D013853:Thioacetamide
keywords: Hepatotoxicity; Oxidative stress; Thioacetamide; ob/ob