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DNA breakage due to metronidazole treatment
D Menéndez1, E Rojas, L A Herrera
1Departamento de Genética y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, P.O. Box 70228, Ciudad Universitaria, 04510, México, D.F., México.
Abstract:
The mutagenicity of metronidazole [1-(hidroxyethyl)-2-methyl-5-nitroimidazole] (MTZ) has been shown in different prokaryotic systems. However, data on human cells are still contradictory. In this study DNA damage was determined by the single cell gel electrophoresis (SCGE) assay, in lymphocytes from 10 healthy subjects treated with therapeutic doses of this drug. Samples were obtained before treatment, as well as 1 and 15 days after ending treatment. Results showed a significant increase of DNA strand breaks 1 day after ending treatment, although, an inverse correlation between the amount of DNA damage and plasma concentrations of MTZ was obtained. Thus, the observed damage may be induced by some MTZ metabolite rather than by the parent drug. Interestingly, the amount of DNA damage returned to basal levels 15 days after ending treatment, except in two individuals. This persistent damage should be further investigated.
Insights
Metronidazole (MTZ) causes DNA damage in human cells, particularly strand breaks in lymphocytes shortly after treatment. This damage may stem from MTZ metabolites and typically resolves within 15 days, though persistent effects warrant further study.
Area of Science:
- Pharmacology
- Genotoxicology
- Human Cell Biology
Background:
- Metronidazole (MTZ) mutagenicity is established in prokaryotes, but its effects on human cells remain debated.
- Therapeutic doses of MTZ are widely used, necessitating a clear understanding of its genotoxic potential in humans.
Purpose of the Study:
- To investigate the mutagenicity of metronidazole (MTZ) in human lymphocytes.
- To assess DNA damage in lymphocytes following therapeutic MTZ treatment.
Main Methods:
- Single cell gel electrophoresis (SCGE) assay used to quantify DNA damage.
- Lymphocytes from 10 healthy subjects analyzed before, 1 day after, and 15 days after MTZ treatment.
Main Results:
- Significant increase in DNA strand breaks observed 1 day post-treatment.
- Inverse correlation between DNA damage and plasma MTZ concentrations suggests metabolite-induced damage.
- DNA damage returned to baseline levels by 15 days in most subjects, with exceptions noted.
Conclusions:
- Metronidazole treatment induces transient DNA damage in human lymphocytes, likely via metabolites.
- Persistent DNA damage in a subset of individuals requires further investigation.
- The SCGE assay is a valuable tool for assessing MTZ genotoxicity in human cells.