Generation of Sanazole Nitro Radicals by Xanthine Oxidase

I. A. Shchepetkin

Institute of Oncology, Tomsk Research Center, Siberian Branch of the Russian Academy of Medical Sciences, Pereulok Kooperativnyi 5, Tomsk, 634001 Russia; E-mail: biomed@mail.tomsknet.ru

Received April 6, 1998

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The formation of sanazole (drug AK-2123) radicals by the xanthine--xanthine oxidase system was studied by spectrophotometry in hypoxygenic (pO₂ = 45 ± 5 mm Hg) and normoxygenic (pO₂ = 150 ± 4 mm Hg) media. At concentrations from 0.1 to 10.5 mM, sanazole dose-dependently increased the rate of cytochrome c reduction in hypoxygenic medium but had no effect on the reaction rate under normoxygenic conditions. The activating influence of sanazole depended on xanthine concentration. At xanthine concentrations from 0.08 to 0.1 mM in hypoxygenic medium, the rate of cytochrome c reduction was increased twofold after the addition of sanazole. Reduction of cytochrome c in the medium without sanazole was completely blocked by superoxide dismutase; addition of sanazole partially restored the blocked reaction. Cytochrome c reduced in the presence of superoxide dismutase and sanazole was oxidized by cytochrome oxidase. The data indicate that in the presence of the xanthine--xanthine oxidase system under hypoxygenic conditions, sanazole can accept electrons and generate nitro radicals which donate electrons to cytochrome c or oxygen.

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KEY WORDS: sanazole, metronidazole, xanthine oxidase, xanthine, hypoxia, nitro radicals, radiosensitizer, nitro compounds

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