title: Studies on hydrazine hepatotoxicity. 2. Biochemical findings.
abstract: Hydrazine causes a dose-related increase in liver triglycerides and in liver weight and causes a decrease in hepatic glutathione. The threshold dose for the toxic effect is around 10 mg/kg, and the optimal effect is seen after a dose of 40 mg/kg. The effect of hydrazine on liver weight and glutathione was detectable within 30 min of dosing, but the elevation of hepatic triglycerides was not detectable until 4 h after dosing. At 24 h after a dose of 60 mg hydrazine/kg, hepatic reduced glutathione was approximately 50% of the control value and triglycerides were about 7 times the normal level. In vitro studies indicated that hydrazine is metabolized by rat liver microsomal enzymes, this being dependent on NADPH and oxygen. Pretreatment of animals with phenobarbital or piperonyl butoxide respectively decreases and increases the hepatotoxicity. Prior depletion of hepatic glutathione by administration of diethyl maleate had no effect on the toxicity. Pyruvate azine, a probable metabolite of hydrazine, is much less toxic than hydrazine itself on a molar basis. These and other results suggest that although hydrazine is metabolized via several routes, the hepatotoxicity may well be due to the parent compound rather than a metabolite.
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D005978:Glutathione / Q000097:blood; D006834:Hydrazines / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D006834:Hydrazines; D014280:Triglycerides; D005978:Glutathione