Evidence for the involvement of a reperfusion injury in galactosamine/endotoxin-induced hepatitis in mice.

Simultaneous intraperitoneal administration of 700 mg/kg galactosamine and 33 micrograms/kg Salmonella abortus equi endotoxin to male NMRI albino mice resulted in fulminant hepatitis as assessed after nine hours by measurement of serum transaminases as well as sorbitol dehydrogenase activities. Intraperitoneal pretreatment of animals with 2 X 100 mg/kg allopurinol, or intravenous pretreatment with 33 kU superoxide dismutase or 1 MU catalase fully prevented hepatitis. Administration of 10 micrograms/kg of the prostacyclin analogue iloprost antagonized liver injury when given simultaneously with galactosamine/endotoxin but did not protect when given 90 min later. Tocopherol or desferal pretreatment of the animals had no significant protective effect. Together with our recent finding that hepatic leukotriene D4 production is likely to be responsible for galactosamine/endotoxin-induced hepatitis we interpret these results as evidence for a leukotriene-induced hepatic ischemia followed by a reperfusion syndrome.