McClain R M, Downing J C
Department of Toxicology and Pathology, Pharmaceutical Research and Development, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Toxicol Appl Pharmacol. 1988 Mar 15;92(3):480-7. doi: 10.1016/0041-008x(88)90187-1.
Reproduction studies were performed with ornidazole, a compound with trichomonacidal activity. Male rats were treated for 61 days prior to mating and female rats were treated for 2 weeks prior to mating and throughout gestation and lactation at doses of 0 (control), 25, 100, and 400 mg of ornidazole/kg/day. A decrease in the pregnancy rate was observed in high-dose rats without altered mating performance. Crossover matings between high-dose treated and control male and female rats showed that male but not female fertility was affected and that the effect on fertility was reversible within several days after the cessation of treatment. Testicular and epididymal weights were not altered in treated male rats. Histopathological examination revealed that spermatogenesis and the testes were normal and that the epididymides of treated male rats contained normal appearing sperm. It is concluded that ornidazole, at high dosages, produces infertility in the male rat; however, unlike many other 5-nitroimidazole compounds which are reported to inhibit spermatogenesis, no effect on spermatogenesis was observed under the conditions of these studies. This in conjunction with the rapid reversibility of infertility suggests that the mode of action of ornidazole involves a rapidly reversible effect on epididymal sperm function.
使用具有杀滴虫活性的化合物奥硝唑进行了生殖研究。雄性大鼠在交配前接受61天的治疗，雌性大鼠在交配前2周以及整个妊娠期和哺乳期接受治疗，剂量分别为0（对照）、25、100和400毫克奥硝唑/千克/天。在高剂量组大鼠中观察到妊娠率下降，但交配性能未改变。高剂量处理的雄性和雌性大鼠与对照大鼠之间的交叉交配表明，雄性而非雌性的生育能力受到影响，且这种对生育能力的影响在停止治疗后的几天内是可逆的。处理后的雄性大鼠睾丸和附睾重量未改变。组织病理学检查显示，精子发生和睾丸正常，处理后的雄性大鼠附睾中含有外观正常的精子。得出的结论是，高剂量的奥硝唑会导致雄性大鼠不育；然而，与许多其他据报道会抑制精子发生的5-硝基咪唑化合物不同，在这些研究条件下未观察到对精子发生的影响。这与不育的快速可逆性相结合表明，奥硝唑的作用方式涉及对附睾精子功能的快速可逆影响。
