ACUTE HEPATIC-FAILURE WITH SWOLLEN MITOCHONDRIA AND MICROVESICULAR FATTY DEGENERATION OF HEPATOCYTES TRIGGERED BY FREE-RADICAL INITIATOR

BACKGROUND: Reye syndrome and acute fatty liver of pregnancy are chara cterized by acute hepatic failure associated with characteristic patho logic changes of hepatocytes, i.e., microvesicular fatty degeneration with severe mitochondrial swelling. Several animal models of these con ditions have been proposed, although none has demonstrated sufficientl y similar laboratory and pathologic features. EXPERIMENTAL DESIGN: A s ingle dose of 2,2'-azobis-(2-amidinopropane) dihydrochloride, a free r adical initiator, 100 mg/kg of body weight, injected intraperitoneally to BALB/c mice induced a transient decrease in hepatic energy charge, liver mitochondrial respiratory activity, and succinate dehydrogenase activity and a transient increase in blood ammonia level, suggesting hepatic failure.RESULTS: The hepatocytes displayed microvesicular fatt y degeneration with severely swollen mitochondria. CONCLUSIONS: This i s the first model of acute hepatic failure with microvesicular fatty d egeneration of hepatocytes. It suggests a role of free radicals in the pathogenesis of certain types of acute hepatic failure.