Drug residue formation from ronidazole, a 5-nitroimidazole. IV. The role of the microflora

Wolf, Frank J.; Alvaro, Raul; Fiorentini, Karen M.; Green, M.; Lu, Anthony Y. H.; Miwa, Gerald T.; Wislocki, Peter G.; Koch, R.; McLafferty, Martha A.; Goldman, Peter

doi:10.1016/0009-2797(83)90038-8

“…Under different experimental conditions leading to enzymatic reduction of this compound, reactive metabolites that bind covalently to protein were produced (81)(82)(83)(84)(85)(86). This covalent binding was effectively prevented by reduced glutathione and cysteine.…”

Section: Free-radical Metabolites Of Metronidazole and Other Nitroimimentioning

confidence: 99%

Mechanism of Toxicity of Nitro Compounds Used in the Chemotherapy of Trichomoniasis

Moreno¹,

Docampo²

1985

Environmental Health Perspectives

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The mechanism of the trichomonicidal activity of metronidazole and other 5-nitroimidazoles appears to depend on the ferredoxin-mediated reduction of their nitro group, with generation of a reactive metabolite or metabolites which interact with DNA leading to a subsequent inhibition of nucleic acid and protein synthesis. Redox cycling of these compounds under aerobic conditions appears to be a detoxification reaction by inhibiting net reduction of the drugs, thereby inhibiting their uptake. On the other hand, redox cycling of nitrofurans or other compounds with more positive reduction potential results in formation of high steady-state concentrations of oxygen-derived metabolites that might be of toxicological significance. It seems likely that reduced metabolites of nitroimidazoles (perhaps through covalent binding to tissue macromolecules and/or thiols depletion) are also involved in the nitroimidazoles' toxic effects to animal tissues and in their mutagenic and carcinogenic action.

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“…Finally, recent studies with ronidazole (81-86) have shed light on the possible mechanism of toxicity of 5nitroimidazoles to animal tissues. Under different experimental conditions leading to enzymatic reduction of this compound, reactive metabolites that bind covalently to protein were produced (81)(82)(83)(84)(85)(86). This covalent binding was effectively prevented by reduced glutathione and cysteine.…”

Section: Free-radical Metabolites Of Metronidazole and Other Nitroimimentioning

confidence: 99%

Mechanism of toxicity of nitro compounds used in the chemotherapy of trichomoniasis.

Moreno¹,

Docampo²

1985

Environ Health Perspect

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The mechanism of the trichomonicidal activity of metronidazole and other 5-nitroimidazoles appears to depend on the ferredoxin-mediated reduction of their nitro group, with generation of a reactive metabolite or metabolites which interact with DNA leading to a subsequent inhibition of nucleic acid and protein synthesis. Redox cycling of these compounds under aerobic conditions appears to be a detoxification reaction by inhibiting net reduction of the drugs, thereby inhibiting their uptake. On the other hand, redox cycling of nitrofurans or other compounds with more positive reduction potential results in formation of high steady-state concentrations of oxygen-derived metabolites that might be of toxicological significance. It seems likely that reduced metabolites of nitroimidazoles (perhaps through covalent binding to tissue macromolecules and/or thiols depletion) are also involved in the nitroimidazoles' toxic effects to animal tissues and in their mutagenic and carcinogenic action.ImagesFIGURE 1.

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Interaction of metronidazole with escherichia coli deoxyribonucleic acid

Malliaros¹,

Goldman²

1991

Biochemical Pharmacology

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Drug residue formation from ronidazole, a 5-nitroimidazole. IV. The role of the microflora

Cited by 9 publications

References 7 publications

Mechanism of Toxicity of Nitro Compounds Used in the Chemotherapy of Trichomoniasis

Mechanism of Toxicity of Nitro Compounds Used in the Chemotherapy of Trichomoniasis

Mechanism of toxicity of nitro compounds used in the chemotherapy of trichomoniasis.

Interaction of metronidazole with escherichia coli deoxyribonucleic acid

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