Cytogenetic study of metronidazole and three metronidazole analogues in cultured human lymphocytes with and without metabolic activation

Gómez‐Arroyo, Sandra; Melchor-Castro, Sara; Villalobos‐Pietrini, Rafael; Meléndez-Camargo, María Estela; Salgado-Zamora, Héctor; Campos-Aldrete, Ma. Elena

doi:10.1016/j.tiv.2003.09.006

Cited by 10 publications

(2 citation statements)

References 25 publications

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“…However, the description of the mutagenic and carcinogenic properties of some 2-and 5-nitroimidazoles have increased interest in the minor mutagenic 4-nitroimidazoles. [8][9][10][11][12][13][14] The electrochemical studies of nitroimidazoles are mainly focused on the analytical determination of some pharmacologically important 5-nitroimidazoles, such as metronidazole, ornidazole, secnidazole, tinidazole, and megazol. [15][16][17][18][19] In addition, cyclic voltammetric studies of nitro radical anions produced from 5-nitroimidazole derivatives have been reported, demonstrating the usefulness of this technique to the study of nitro free radicals.…”

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confidence: 99%

Voltammetric Behavior of a 4-Nitroimidazole Derivative

Yáñez

Pezoa

Rodriguez

et al. 2005

J. Electrochem. Soc.

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A new synthesized compound, 1-methyl-4-nitro-2-hydroxymethylimidazole ͑4-MNImOH͒, was electrochemically reduced at the mercury electrode in aqueous, mixed, and aprotic media. In an aqueous medium, only one voltammetric peak was observed because of the four-electron, four-proton reduction of the nitro group to the hydroxylamine derivative in the 2-12 pH range. For the mixed and nonaqueous media, it was possible to observe a reversible couple due to the first one-electron reduction step of the nitro group to the nitro radical anion.The nitro radical anion decays by a disproportionation reaction in mixed media and by dimerization in a nonaqueous medium. Both disproportionation and dimerization rate constants, k 2 , were determined according to Olmstead's approach, obtaining a value of 1460 ± 110 M −1 s −1 in aprotic medium. In mixed media, the values were dependent both on pH and on the nature of the cosolvent.After comparison of 4-MNImOH with the parent compound, 4-nitroimidazole, we concluded that the substitution with 1-methyl and 2-hydroxymethyl produces a more easily reducible nitro compound and a less stable nitro radical anion than the unsubstituted 4-nitroimidazole. According to the electrochemical results, the 4-MNImOH derivative would be more suitable for enzymatic reduction and less toxic to the host than 4-nitroimidazole.In the last decades, nitroimidazoles have been the source of many investigations because of their properties as antibiotics, radiosensitizers, and antiprotozoans. 1-3 The biological activity of nitroimidazoles is dependent on the nitro group reduction process due to the formation of active intermediate species that interact with DNA and cause biochemical damage. The reduction of these compounds can follow two different routes depending on whether the medium is aerobic or anaerobic, 4,5 however, both routes share a common first step, i.e., the one-electron reduction of the nitro group to form the nitro radical anion ͑RNO 2 •− ͒. Consequently, RNO 2 •− is a key intermediate in the biological activity, and the understanding of its behavior is a permanent challenge for these type of compounds.Three types of nitroimidazole derivatives have been currently used, namely, 2-, 4-, and 5-nitrosubstituted derivatives; however, there are still no conclusive results about the incidence of the nitro substitution in their biological activity. A study on the reduction of 2-, 4-and 5-nitroimidazole drugs by hydrogenase 1 in Clostridium pasteurianum 6 revealed that the rate of reduction of the nitroimidazole compounds correlated with their one-electron reduction potential. However, the reduction rates for the drugs did not correlate with the antibacterial activity against Clostridium pasteurianum, suggesting that other factors are also important for determining the antimicrobial potencies of these compounds. Another study on the activity of nitroimidazoles against Trichomonas vaginalis 7 revealed that the potency of this activity follows the order 5-nitroimidazole Ͼ 2-nitroimidazole Ͼ 4-nitroimidazole. How...

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confidence: 99%

Voltammetric Behavior of a 4-Nitroimidazole Derivative

Yáñez

Pezoa

Rodriguez

et al. 2005

J. Electrochem. Soc.

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“…Ornidazole is known to act through its reductive activation of the nitro groups 10 by susceptible microorganisms in high doses metronidazole has been reported to be carcinogenic in rodents and mutagenic in bacteria. 15,16 Presence of nitro group is has been suggested to be responsible for its mutagenic and genotoxic activity. 7,10 On the other hand metronidazole has been reported to be non-genotoxicity in mice 6 and human 17 studies.…”

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confidence: 99%

Genotoxic evaluation of ornidazole and secnidazole in albino mice: an experimental study

Revankar

Vedavathi

2014

Int J Basic Clin Pharmacol

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A sub‐acute study of metronidazole toxicity assessed in Egyptian Tilapia zillii

Khalil

Mahmoud

Zahran

et al. 2007

J of Applied Toxicology

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Metronidazole (MTZ), an antiparasitic and antibacterial compound, is one of the world's most widely used drugs. Despite being considered as a rodent mutagen and a carcinogen, it is still widely used in humans for the treatment of infections with anaerobic organisms. Therefore, the main objective of the current study was to evaluate the in vivo toxicity of MTZ using the micronucleus (MN) assay and random amplified polymorphism DNA (RAPD-PCR) analysis as well as histopathological examination in Tilapia zillii. Moreover, the protective effect of vitamin C (VitC) against toxicity of MTZ was investigated in the present study. Fish were treated with three doses of MTZ (5, 10 and 20 mg l(-1)) alone or in combination with VitC (200 mg kg(-1) food) at several time intervals (2 days, 7 days and 14 days). The results of the present study showed a significant effect of MTZ on micronucleus formation and changes in polymorphic band patterns as well as induction of different histopathological alterations in Tilapia zillii. The effects of the drug were reduced when fish were exposed to a combination of MTZ and VitC.

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Cytogenetic study of metronidazole and three metronidazole analogues in cultured human lymphocytes with and without metabolic activation

Cited by 10 publications

References 25 publications

Voltammetric Behavior of a 4-Nitroimidazole Derivative

Voltammetric Behavior of a 4-Nitroimidazole Derivative

Genotoxic evaluation of ornidazole and secnidazole in albino mice: an experimental study

A sub‐acute study of metronidazole toxicity assessed in Egyptian Tilapia zillii

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