Reproductive and Cytogenetic Toxicity of Metronidazole in Male Mice

Abstract

The purpose of this study was to examine the effects of metronidazole (500 mg/kg b.wt. daily by gavage for 14 consecutive days) on male fertility, haematopoiesis and genotoxic affinity. Mature male Swiss mice were treated with metronidazole and divided into 3 groups each with 10 animals, examined after 2 weeks, 1 and 2 months from the onset of drug administration. The results demonstrated that metronidazole significantly (PϽ0.05) decreased the weight of the testes, epididymides and accessory sexual organs (seminal vesicles and prostates) after one month from the onset of treatment. While accessory sexual organ weights were restored after 2 months from onset of treatment, the decrease in testes and epididymides weights persisted until 2 months later. The deleterious effects of metronidazole on reproductive organ weights might be due to a decrease in testosterone level after 2 weeks, and 1 and 2 months from the onset of treatment. Metronidazole induced a significant decrease in motile sperm and an increase in abnormal sperm after 1 month. The viability of sperm was normal after 2 months. Metronidazole induced anaemia characterized by decreased erythrocyte and leukocytic counts, haemoglobin content and haematocrit %. The ability of oral metronidazole administration to induce genotoxic damage in somatic cells of mice was evaluated using mitotic index, micronuclei and chromosomal aberration. A significant reduction in mitotic activity was observed two weeks from the onset of drug administration, restoration occured after one month. A significant and persistence increase in the frequency of chromosomal aberration and micronucleus was observed at all periods of the experiment. In conclusion, the results of this study indicate that 1) metronidazole (500 mg/kg by gavage) for 14 days caused a harmful effect on male fertility in mice after one and two months from start of administration, 2) metronidazole induced anaemia after one month from start of administration, 3) metronidazole at this high dose level (3 times the therapeutic dose in mice) has the ability to induce genotoxic effects in somatic cells.

Micronucleus induction by metronidazole in rat vaginal mucosa

“…Previous reports indicate that MTZ is genotoxic in mouse somatic cells [el-Nahas and el-Ashmawy, 2004], and that chronic treatment with MTZ is carcinogenic in rodents [Sloan et al, 1983;A-Kareem et al, 1984;Fahrig and Engelke, 1997]. In the present study, relatively shortterm treatment of rats with MTZ increased PMNC frequencies, but the increase was significant only with the highest MTZ dose tested (100 mg/kg), a dose that was greater than MTZ doses that were genotoxic in other assays and greater than human therapeutic doses.…”

“…Previous studies have demonstrated the genotoxicity of MTZ in rodents [Neal and Probst, 1984;Mudry et al, 1994;Fahrig and Engelke, 1997;el-Nahas and el-Ashmawy, 2004]; however, rats have high levels of nitroreductases in their intestinal microflora, especially when compared with humans, and this activity could be responsible for to the genotoxicity of MTZ in rodents when the compound is administered orally [Fahrig and Engelke, 1997]. In the present study, MTZ was administered topically to the rat vagina, so the compound may not have been metabolized in the same way as occurs when MTZ is administered orally or parenterally.…”

“…MTZ and body fluids from MTZ-treated humans and mice are mutagenic in bacteria [Legator et al, 1975;Speck et al, 1976;Koch et al, 1981]. MTZ is genotoxic in vitro in short-term tests and oral administration of MTZ increases abnormal anaphases, chromosome aberrations, and micronucleus (MN) frequency in vivo [Mudry et al, 1994;Elizondo et al, 1996;el-Nahas and el-Ashmawy, 2004]. Urtasun et al [1983] found that MTZ sensitized tumor cells to radiotherapy, suggesting that MTZ can contribute to the DNA damage caused by therapeutic radiation.…”

β-Caryophyllene as putative male contraceptive: enhances spermatogenesis but not spermiogenesis in albino rats

“…), undulated tails (und.) and bent trails; c sperms with coiled flagellum (coiled), and sperms with tails with ansa (ansa) genotoxic, cytotoxic, and mutagenic activity on the spermatogonia (El-Nahas and El-Ashmawy, 2004). MTZ results in decreasing testicular and epididymal weights and decreasing testicular spermatid and epididymal sperm counts (McClain et al, 1989).…”

Lactoferrin as an Adjunctive Agent in the Treatment of Bacterial Infections Associated with Diabetic Foot Ulcers

“…However, metronidazole is toxic, causing nausea, vomiting, abdominal pain and other effects. In addition, it might be carcinogenic to patients when used at high doses and/or as a long-term treatment, evidenced by DNA breakages and chromosome aberrations caused by this drug in cultured cells, and by its carcinogenic effects in animal tests (Roe, 1983;Dobias et al, 1994;El-Nahas & El-Ashmawy, 2004;Kapoor et al, 1999;Mudry et al, 1994).…”