Activation of PPARα-catalase pathway reverses alcoholic liver injury via upregulating NAD synthesis and accelerating alcohol clearance.

ABSTRACT: Alcohol metabolism in the liver simultaneously generates toxic metabolites and disrupts redox balance, but the regulatory mechanisms have not been fully elucidated. The study aimed to characterize the role of PPARα in alcohol detoxification. Hepatic PPARα and catalase levels were examined in patients with severe alcoholic hepatitis. Mouse studies were conducted to determine the effect of PPARα reactivation by Wy14,643 on alcoholic hepatotoxicity and how catalase is involved in mediating such effects. Cell culture study was conducted to determine the effect of hydrogen peroxide on cellular NAD levels. We found that the protein levels of PPARα and catalase were significantly reduced in the livers of patients with severe alcoholic hepatitis. PPARα reactivation by Wy14,643 effectively reversed

SUBMITTER: Yue R 

PROVIDER: S-EPMC8437058 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature