Mechanism of allyl formate-induced hepatotoxicity in rainbow trout

Hepatotoxicity of allyl formate (AF) was studied in trout, to characterize the response of the teleost liver to a mammalian periportal hepatotoxicant. A dose-dependent decrease in liver nonprotein sulfhydryl (NPSH) concentration was observed at 3, 6, and 24 hr following 9.5, 28, and 95 mg/kg) AF with maximal depression seen at 6 hr (51, 40, and 29% control, respectively). Further evidence for glutathione (GSH) protection against AF toxicity was seen when diethylmaleate, a GSH depleting agent (0.6 ml/kg ip), administered 30 min prior to AF (9.5 and 28 mg/kg), increased AF hepatotoxicity (10-fold shift in the dose-response effect on SGPT). Also, N-acetyl-L-cysteine (150 mg/kg ip), a GSH precursor, protected liver against AF toxicity when injected 5 min prior to and 1, 5, and 9 hr after AF (28 and 95 mg/kg). Pyrazole (375 mg/kg ip), an alcohol dehydrogenase inhibitor, given 4 hr before AF (95 mg/kg), attenuated the histopathological effect of AF. These results indicate that AF, once bioactivated by alcohol dehydrogenase, causes significant toxicity in trout liver. GSH protects against AF-induced effects since greater than 50% decreases in liver GSH are required before toxicity is expressed.