Production of superoxide during the metabolism of nitrazepam
- 1 January 1984
- journal article
- research article
- Published by Taylor & Francis in Xenobiotica
- Vol. 14 (10), 785-794
- https://doi.org/10.3109/00498258409151477
Abstract
1. Nitrazepam is metabolized in both humans and rats to 7-amino-nitrazepam indicating that this drug is reduced to a number of metabolic intermediates including several free radical species. 2. When rat-hepatic microsomes are incubated with NADPH in the presence of nitrazepam, its nitro anion free radical was observed under anaerobic conditions. In the presence of oxygen, this free radical reduced oxygen giving nitrazepam and superoxide. 3. 7-Nitroxyl-nitrazepam was produced by the chemical oxidation of 7-amino-nitrazepam using m-chloroperbenzoic acid. Reaction of this reactive free radical with hepatic microsomes led to the covalent spin labelling of microsomal protein. This phenomenon was also observed by the enzymic oxidation of 7-amino-nitrazepam with hepatic microsomes, obtained from a phenobarbital-induced rat, in the presence of a NADPH-generating system. 4. With the generation of superoxide and hydrogen peroxide (arising from the dismutation of superoxide), it is not surprising that nitrazepam-enhanced lipid peroxid-ation was demonstrated by monitoring the production of lipid peroxyl radicals using spin-trapping techniques.This publication has 16 references indexed in Scilit:
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