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Title 

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

Authors 

Young Suk WonJ W SongJ H LimM Y LeeOg Sung MoonHyoung-Chin KimH Y SonH J Kwon

Publisher 

Elsevier

Issue Date 

2016

Citation 

Toxicology and Applied Pharmacology, vol. 291, no. 0, pp. 38-45

Keywords 

Hepatotoxicityob/obOxidative stressThioacetamide

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 [14C]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.

ISSN 

0041-008X

Link 

http://dx.doi.org/10.1016/j.taap.2015.12.001

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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