Molecular Pharmacology, Vol 19, 146-152, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Involvement of Radical Species in the Oxidation of Aminopyrine and 4-Aminoantipyrine by Cumene Hydroperoxide in Rat Liver Microsomes

¹ Biochemistry Department, The University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Spectral changes observed during the microsomal oxidation of aminopyrine by cumene hydroperoxide have demonstrated the formation of the aminopyrine radical prior to, and concomitant with, the formation of antipyrine red. The latter chromophore is the oxidation product of 4-aminoantipyrine in several systems, including microsomes with cumene hydroperoxide, which generate one-electron oxidants. The spin-trap nitrosobenzene strongly inhibited not only the cumene hydroperoxide-supported oxidation of aminopyrine and its metabolite, but also the oxygen utilization of microsomes stimulated by this hydroperoxide. Thus, efficient trapping by nitrosobenzene of reactive organic radicals derived from cumene hydroperoxide inhibits their subsequent reactions, i.e., substrate oxidation and initiation of lipid peroxidation. These cumene hydroperoxide-dependent activities of microsomes were significantly inhibited by micromolar concentrations of metyrapone and also by known substrates of cytochrome P-450, thus demonstrating the essential role of this hemeprotein in these reactions.

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