IN-VITRO MICROSOMAL METABOLISM OF HYDRAZINE

1. It has been demonstrated that hydrazine is metabolized by rat liver enzymes located in the microsomal fraction. This metabolism was reduced in the absence of oxygen or NADPH and was increased by NADH in the presence of NADPH. 2. Microsomal enzyme inhibitors, piperonyl butoxide and metyrapone, significantly inhibited hydrazine metabolism but glutathione had no affect and was not depleted. 3. In addition to P450, flavin monooxygenase may also be involved in catalysing the microsomal metabolism of hydrazine. 4. Liver microsomes prepared from either beta-naphthoflavone, acetone or the isoniazid-pretreated rat did not show a significant increase in hydrazine metabolism compared with microsomes from the control rat. However, although phenobarbitone pretreatment increased overall microsomal hydrazine metabolism this was not increased relative to P450 content. 5. Hydrazine metabolism was 20-70% lower in human microsomes prepared from three individuals compared with the control rat. 6. Hydrazine is also metabolized by rat liver mitochondria but the monoamine oxidase inhibitors clorgyline and pargyline do not significantly decrease this.