Studies on hydrazine hepatotoxicity. 2. Biochemical findings

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Abstract
Hydrazine caused a dose-related increase in liver triglycerides and weight and hepatic glutathione in rats. The threshold dose for the toxic effect was .apprx. 10 mg/kg, and the optimal effect was 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 .apprx. 50% of the control value and triglycerides were .apprx. 7-fold the normal level. In vitro studies indicated that hydrazine was metabolized by rat liver microsomal enzymes, this being dependent on NADPH and O2. Pretreatment of animals with phenobarbital or piperonyl butoxide, respectively, decreased and increased 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, was less toxic than hydrazine itself on a molar basis. These and other results suggested that although hydrazine was metabolized via several routes, the hepatotoxicity may have been due to the parent compound rather than a metabolite.

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