Role of neutrophils in hepatotoxicity induced by oral acetaminophen administration in rats

Acetaminophen (APAP) is a common analgesic and antipyretic compound which, when administered in high doses, has been associated with significant morbi dity and mortality, secondary to hepatic toxicity. To date, the mechanism(s ) whereby APAP induces liver injury remains to be delineated. This study in vestigated the potential role of neutrophils as contributors to liver injur y in rats administered sublethal doses of APAP. Oral APAP administration (6 50 mg/kg) was associated with increases in serum alanine transaminase (ALT) levels indicating biochemical evidence of significant liver damage. Furthe rmore, histological analyses verified significant hepatocellular necrosis a s well as enhanced myeloperoxidase staining in these liver specimens. Howev er, if animals were pretreated with antineutrophil sera prior to APAP admin istration, neutrophil counts remained depressed, ALT levels were significan tly decreased, and the degree of liver injury was attenuated on a histologi cal level, Taken together these data suggest that neutrophils mediate, at l east in part, the hepatotoxic effects of oral acetaminophen administration in rats. (C) 1998 Academic Press.