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.
Droy
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BF
Department of Pharmacology and Toxicology, West Virginia University School of Medicine, Morgantown 26505.
Davis
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ME
Hinton
D E
DE
D000111:Acetylcysteine / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000444:Aldehyde Dehydrogenase / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005561:Formates / Q000633:toxicity*; D005563:Formic Acid Esters / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis / Q000502:physiology; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008298:Maleates / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000032:analysis; D014337:Trout
D005561:Formates; D005563:Formic Acid Esters; D008298:Maleates; D013438:Sulfhydryl Compounds; C034499:allyl formate; D000444:Aldehyde Dehydrogenase; D000410:Alanine Transaminase; C014476:diethyl maleate; D005978:Glutathione; D000111:Acetylcysteine