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 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.
Natural dietary antioxidants are extensively studied for their ability to protect cells from miscellaneous damages.Origanum majoranaL., Lamiaceae, is a potent antioxidant. The effect of administration ofO. majorana(volatile oil, alcoholic and aqueous extracts) on oral administration of lead acetate in the diet of mice at concentration 0.5% (W/W) for one month were studied by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine, histopathological changes of the liver and kidney and genotoxicity including, rate of micronucleus and chromosomal aberrations in bone marrow cells. Mice were treated with the 3 different forms ofO. majorana, one month before and maintained with lead acetate administration. The 3 forms ofO. majoranainduced a significant decrease in serum activities of transaminases (AST & ALT), ALP, urea and creatinine and improved the liver and kidney histology in comparison with lead acetate treated group. Alcoholic extracts ofO. majoranasignificantly reduced the rate of micronucleus, number of aberrant cells and different kinds of chromosomal aberrations. Volatile oil extract significantly reduced the rate of micronucleus and chromosomal fragments. Aqueous extract and volatile oil also ofO. majoranasignificantly reduced number of gaps, ring chromosome and stickiness. It could be concluded thatO. majoranaplays an important role in ameliorating liver and kidney functions and genotoxicity induced by lead toxicity.