Teratogenic evaluation of metronidazole and ornidazole using <i>Drosophila melanogaster</i> as an experimental model

Palermo, Ana María; Reynoso, A.S.; Nigro, Marcela M. López; Carballo, Marta A.; Mudry, Marta Dolores

doi:10.1002/bdra.20008

Cited by 10 publications

(4 citation statements)

References 20 publications

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“…When we analyze the potential metronidazole genotoxicity we found differences in micronucleus frequencies between the control groups and the experimental groups which had received metronidazole for all the mouse strains used. These findings agree with previous reports described in the literature (Dobiàs et al, 1994, Cavas andErgene-Gozukara, 2005) and widely studied in other models and experimental designs (Mudry et al, 1994;López Nigro et al, 2003;Palermo et al, 2004;Mudry et al, 2007).…”

supporting

confidence: 93%

The bone marrow micronucleus test and metronidazole genotoxicity in different strains of mice (Mus musculus)

Abrevaya¹,

Carballo²,

Mudry³

2007

Genet. Mol. Biol.

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The mouse (Mus musculus) bone marrow micronucleus test was carried out using 24 outbred National Institutes of Health (NIH) mice, 24 inbred Swiss Webster (CFW) mice and 20 inbred Bagg albino/color locus Jackson (BALB/cJ) mice. The mice in the experimental group (n = 32) were injected intraperitoneally with 133 mg kg -1 of metronidazole parenteral solution and the control group consisted of mice (n = 36) which had not been injected with metronidazole. There was no significant difference (p > 0.05) between the sexes regarding the micronucleus frequency in either the experimental or the control group. When the Mn frequencies of the three strains were compared, the results for the CFW and BALB/cJ strains did not differ statistically (p > 0.05) for either the experimental or control groups but there were significant (p < 0.05) differences between the CFW and NIH strains and the NIH and BALB/cJ strains for the experimental and control groups, with the NIH strain always showing the highest micronucleus frequency. Our results also show that metronidazole was possible genotoxic agent because it produced a significant increase (p < 0.05) in the micronucleus frequency of the experimental group as compared to the control group for all the three mouse strains tested.

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supporting

confidence: 93%

The bone marrow micronucleus test and metronidazole genotoxicity in different strains of mice (Mus musculus)

Abrevaya¹,

Carballo²,

Mudry³

2007

Genet. Mol. Biol.

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“…Plants have developed an enzymatic (SOD, CAT, ascorbate peroxidase) and nonenzymatic (glutathione, ascorbate, carotenoids) antioxidant system to keep the concentrations of harmful ROS lower [33]. The controversial results of MTZ genotoxic effects cited in the literature could be partially because of metabolic differences and the redox status of the tissue used in each experimental model [28,29,39,40]. In the present study, antioxidant defenses responded to MTZ toxicity by increasing SOD and CAT activity, increasing GSH levels, and changing the AA:DHA ratio.…”

Section: Discussionmentioning

confidence: 99%

“…The observed differences between tissues may be the result of differences in oxygen consumption. The controversial results of MTZ genotoxic effects cited in the literature could be partially because of metabolic differences and the redox status of the tissue used in each experimental model [28,29,39,40].…”

Section: Discussionmentioning

confidence: 99%

Oxidative damage and antioxidant response of Allium cepa meristematic and elongation cells exposed to metronidazole

Andrioli

Sabatini

Mudry

et al. 2012

Environmental Toxicology and Chemistry

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The toxicity of metronidazole (MTZ) in meristematic and elongation zones of Allium cepa roots was analyzed for 30 h of exposition. Toxic effects were evaluated by lipid peroxidation (content of thiobarbituric‐reactive substances [TBARS]), reduced glutathione (GSH) levels, ascorbate acid and dehydroascorbate acid content, and enzymatic activities of superoxide dismutase and catalase. The root zones showed differentiated susceptibility to MTZ. In the elongation zone, MTZ induced an increase of TBARS content and a significant rise in GSH levels, whereas in the meristematic zone, lipid peroxidation was not observed and all antioxidant defense parameters analyzed were significantly increased. These results indicate that MTZ exposure induced oxidative stress in A. cepa roots, and that the antioxidant defenses in the meristematic zone are more efficient compared with the elongation zone, which is probably related to higher oxidative metabolism of meristematic tissue. Environ. Toxicol. Chem. 2012; 31: 968–972. © 2012 SETAC

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“…In the last 20 years MTZ has been re-evaluated regarding its potential cytotoxicity, genotoxicity, reproductive and developmental toxicity in different animal and vegetal in vivo/in vitro model systems [6][7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Metronidazole Induced DNA Damage in Somatic Cells of Drosophila melanogaster

Palermo¹,

Mudry

2013

CDS

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The standard version of the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster was employed in order to evaluate the genotoxic potential of metronidazole (MTZ) as a function of exposure concentration. MTZ was administered by chronic feeding of 3-day-old larvae with the parenteral solution at 0, 500, 1000 and 2000 μg/ml until pupation. The marker-heterozygous progeny (mwh+/+flr3) with phenotypically wild-type wings was analyzed. Non significant differences were found between control and each MTZ concentration tested for single small spots (SSS) frequencies. Large single spots (LSS) and twin spots (TS) were significantly increased with the higher dose. MTZ treatments with 1000 and 2000 μg/ml also significantly increased the frequency of Total spots. These findings suggest that MTZ is genotoxic in the present experimental conditions and induces recombinagenesis and/or gene conversion, two major mechanisms that cause loss of heterocigosity and could play an important role in tumorigenesis and carcinogenesis processes.

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Teratogenic evaluation of metronidazole and ornidazole using Drosophila melanogaster as an experimental model

Cited by 10 publications

References 20 publications

The bone marrow micronucleus test and metronidazole genotoxicity in different strains of mice (Mus musculus)

The bone marrow micronucleus test and metronidazole genotoxicity in different strains of mice (Mus musculus)

Oxidative damage and antioxidant response of Allium cepa meristematic and elongation cells exposed to metronidazole

Metronidazole Induced DNA Damage in Somatic Cells of Drosophila melanogaster

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