Enhanced hepatotoxicity by acetaminophen in Vanin-1 knockout mice is associated with deficient proliferative and immune responses.

ABSTRACT:

Background and aims

Pretreatment with clofibrate, a peroxisome proliferator-activated receptor alpha (PPARa) agonist, protects mice from acetaminophen (APAP) injury. Protection is not due to alterations in APAP metabolism and is dependent on PPARa expression. Gene array analysis revealed that mice receiving clofibrate have enhanced hepatic Vanin-1 (Vnn1) gene expression, a response that is also PPARa dependent.

Methods

We examined the role of Vnn1 by comparing the responses of Vnn1 knockout and wild-type mice following APAP hepatotoxicity. APAP metabolism, hepatotoxicity, and compensatory hepatocyte proliferation and immune responses were assessed.

Results

Vnn1 knockout mice are more susceptible to APAP hepatotoxicity despite no differences in hepatic glutathione cont

SUBMITTER: Ferreira DW 

PROVIDER: S-EPMC4788548 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature