Reproductive and cytogenetic toxicity of metronidazole in male mice.
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 (P<0.05) 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 occurred 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.
el-Nahas
Abeer F
AF
Departments of Genetics and Pharmacology, Faculty of Veterinary Medicine Alexandria University, Egypt. abeerelnahas@hotmail.com
el-Ashmawy
Ibrahim M
IM
D000740:Anemia / Q000097:blood / Q000139:chemically induced; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects; D004906:Erythrocyte Count; D005298:Fertility / Q000187:drug effects*; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D008940:Mitotic Index; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D012669:Seminal Vesicles / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D000890:Anti-Infective Agents; D008795:Metronidazole; D013739:Testosterone