Effect of Metronidazole on Fertility and Testicular Function in Male Rats

McClain, R.M.; Downing, John C.; Edgcomb, John

doi:10.1093/toxsci/12.3.386

Cited by 4 publications

(4 citation statements)

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“…Previous studies have shown that a single oral dose of metronidazole 250 mg/kg drastically reduced testicular weight and resulted in infertility in rats after 2–3 weeks, lasting for 3–4 weeks (Patanelli 1975). High doses of metronidazole produced infertility in the male rat (McClain et al 1989).…”

Section: Discussionmentioning

confidence: 99%

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Reproductive and Cytogenetic Toxicity of Metronidazole in Male Mice

El‐Nahas

El-Ashmawy

2004

Basic Clin Pharma Tox

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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.

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Section: Discussionmentioning

confidence: 99%

“…The prerequisite for this is nitroreductases which are capable of reducing the nitro group in animal organs and tissues (Schmid & Schmid 1999). Metronidazole induced a reversible bone marrow depression and effects on male fertility (El‐Ashmawy 1988; McClain et al 1989; Grover et al 2001).…”

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confidence: 99%

Reproductive and Cytogenetic Toxicity of Metronidazole in Male Mice

El‐Nahas

El-Ashmawy

2004

Basic Clin Pharma Tox

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“…It is also inactive in chromosome aberration tests using human lymphocytes or bone marrow cells [Salamanca-Gomez et al, 1980;Elizondo et al, 1994]. At high doses (400 mg/kg b.w./day and higher), metronidazole produces germ-cell depletion in rat seminiferous tubules, reduced testicular weights, and low spermatid and sperm counts [McClain et al, 1989].…”

Section: Metronidazolementioning

confidence: 99%

Unscheduled DNA synthesis assay in mammalian spermatogenic cells: An update

Sotomayor

Sega

2000

Environ. Mol. Mutagen.

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“…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). This drug also causes the production of morphologically abnormal immature sperms with impaired flagellum and/or heads (Mudry et al, 2007) and causes severe degeneration of the seminiferous epithelium.…”

Section: Introductionmentioning

confidence: 99%

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

2015

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It is Cannabis-derived cannabinoid receptors type 2 (CB2R) agonist. CBR2 are expressed in germ cells within the testes. The aim of this study was to investigate the effect of b-Car on the male rat body weight, sex organ weight, sperm count, motility and morphology, and on the histology and the ultrastructure of the testes and the cauda epididymides. Moreover, we compared these effects with the results of the reversible infertility inducer: metronidazole (MTZ). Sexually mature male rats were divided into five groups that received intraperitoneal injections of 10 mg/kg b-Car, 40 mg/kg MTZ, distilled water, tween 80 in normal saline solution (10 % v/v), or did not receive any treatment for an experimental period of 30 days. Cauda epididymal sperm suspensions were used to assess the sperm count, motility, and morphology. Histological and ultrastructural studies were performed on testes and cauda epididymides. Treatment with b-Car (10 mg/kg, i.p.) significantly increased the final body weight, but did not affect the sex organ weight. It resulted in a significant decrease in cauda epididymal sperm count, percentages of motile sperms, and sperms with normal morphology. Nevertheless, it neither affected the histology nor the ultrastructure of the testes or the cauda epididymides of the treated rats. As a CB2R, b-Car could be a promising natural male contraceptive, because 30-day treatment with 10 mg/kg b-Car did not affect spermatogenesis but negatively affected spermiogenesis.

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Effect of Metronidazole on Fertility and Testicular Function in Male Rats

Cited by 4 publications

References 0 publications

Reproductive and Cytogenetic Toxicity of Metronidazole in Male Mice

Reproductive and Cytogenetic Toxicity of Metronidazole in Male Mice

Unscheduled DNA synthesis assay in mammalian spermatogenic cells: An update

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

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