Mechanism of Metabolic Activation of Nitroimidazoles
5-Nitroimidazoles are highly effective therapeutic agents (1) against a variety of anaerobic bacteria and protozoa (Table 1). For this reason, the medicinal use of these agents has been explored in humans and in food-producing animals. For example, metronidazole (1-hydroxyethyl-2-methyl-5-nitroimidazole) is used in human therapy because of its proven activity against trichomoniasis as well as its prophylactic and therapeutic efficacy against a wide range of gram positive anaerobic bacteria (2, 3). Ronidazole [l-methyl-5-nitroimidazole-2-yl)-methylcarbamate] is a highly effective drug for the treatment of turkey blackhead and swine dysentery. However, as a class, 5-nitroimidazoles are genotoxic. Various studies have demonstrated the critical importance of the reduction of the nitro group in their cytotoxicity, mutagenicity, carcino-genicity and interaction with DNA (2–5). To investigate the mechanism of metabolic activation of 5-nitroimidazoles, the covalent binding of ronidazole to proteins has been extensively studied in rats.
KeywordsNitro Group Covalent Binding Reactive Metabolite Protein Adduct Carbamic Acid
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