Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced hepatotoxicity via increased oxidative damage.

ABSTRACT: Acetaminophen (APAP) overdose induces acute liver damage and failure via reactive oxygen species production and glutathione (GSH) depletion. Methionine sulfoxide reductase B1 (MsrB1) is an antioxidant selenoenzyme that specifically catalyzes the reduction of methionine R-sulfoxide residues. In this study, we used MsrB1 gene-knockout mice and primary hepatocytes to investigate the effect of MsrB1 on APAP-induced hepatotoxicity. Analyses of histological alterations and serum indicators of liver damage showed that MsrB1^-/- mice were more susceptible to APAP-induced acute liver injury than wild-type (MsrB1^+/+) mice. Consistent with the in vivo results, primary MsrB1^-/- hepatocytes displayed higher susceptibility to APAP-induced cytotoxicity than MsrB1^+/+</

SUBMITTER: Kim KY 

PROVIDER: S-EPMC5807074 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature