Metabolic modulation of acetaminophen-induced hepatotoxicity by osteopontin.

ABSTRACT: Induction of osteopontin (OPN), a well-known pro-inflammatory molecule, has been observed in acetaminophen (APAP)-induced hepatotoxicity. However, the precise cell source for OPN induction and its role during APAP-induced hepatotoxicity has not been fully explored. By employing a hepatotoxic mouse model induced by APAP overdose, we demonstrate that both serum and hepatic OPN levels were significantly elevated in response to APAP treatment. Our in vivo and in vitro studies clearly indicated that the induced expression of hepatic OPN was mainly located in necrosis areas and produced by dying or dead hepatocytes. Functional experiments showed that OPN deficiency protected against the APAP-induced liver injury by inhibiting the toxic APAP metabolism via reducing the expression of the cytochrom

SUBMITTER: Wen Y 

PROVIDER: S-EPMC6474212 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature