Diet Restriction Inhibits Apoptosis and HMGB1 Oxidation and Promotes Inflammatory Cell Recruitment during Acetaminophen Hepatotoxicity

Daniel James Antoine, Dominic P Williams, Anja Kipar, Hugh Laverty, and B Kevin Park

Drug induced liver injury (DILI) is a major clinical concern and a leading cause of acute liver failure (ALF). Acetaminophen is a widely used analgesic which is safe at therapeutic doses. Acetaminophen hepatotoxicity following overdose contributes to a significant proportion of cases of ALF worldwide. While biochemical events leading to acetaminophen hepatotoxicity are well-defined, little is known about the cellular mechanism linking metabolic activation to clinical outcome. In this study, Antoine et al. investigated the effect of dietary restriction on cellular mechanisms during acetaminophen hepatotoxicity. Their findings indicate the inhibition of caspase driven apoptosis and HMGB1 oxidation by ATP depletion from fasting, promotes an inflammatory response during drug-induced hepatotoxicity. This work may aid the development of intervention therapies for cases of acetaminophen overdose and could improve the clinical management of drug induced liver injury.

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Posted by MolMed Admin on Nov 4, 2010 12:00 AM CDT