Tsutsumi S, Tanaka T, Gotoh K, Akaike M
Drug Development Research Laboratories, Hoechst Japan Limited, Saitama, Japan.
J Toxicol Sci. 1995 Aug;20(3):351-65. doi: 10.2131/jts.20.351.
Pyridoxine (PN) was intraperitoneally given at 250 and 500 mg/kg to male rats for 2, 4, or 6 weeks, and its effects on male fertility evaluated in terms of the optimal treatment period and detection parameters. Animals of all PN groups showed depression of body weight gains from week I of treatment onwards, significant at all but the 250 mg/kg 2 week administration I week time point. After 2 weeks treatment, the testes demonstrated only very slight histopathological changes. The 4- and 6-week treatments caused decreased spermatozoal motility and some histopathological changes in the testes including degeneration of germinal epithelial cells with both doses and also decreases in the fertility index and mean velocity of sperm, reduction in the testes and epididymides weights, and changes in testicular proteins. In the animals undergoing a 4-week recovery period following 4 or 6 weeks exposure, changes disappeared with the 250 mg/kg dose, but still remained with 500 mg/kg. From these findings, it is concluded that a treatment period of 4 weeks is sufficient for evaluation of drug effects on male fertility and that histopathology can detect the slightest toxic effects on the testis.
将250毫克/千克和500毫克/千克的吡哆醇(PN)腹腔注射给雄性大鼠,持续2、4或6周,并根据最佳治疗期和检测参数评估其对雄性生育能力的影响。从治疗第1周起,所有PN组动物的体重增加均出现下降,除250毫克/千克剂量给药2周、第1周时间点外,其他各时间点均有显著下降。治疗2周后,睾丸仅表现出非常轻微的组织病理学变化。4周和6周的治疗导致精子活力下降,睾丸出现一些组织病理学变化,包括两个剂量组的生精上皮细胞变性,以及生育指数和精子平均速度降低、睾丸和附睾重量减轻以及睾丸蛋白质变化。在接受4周或6周暴露后有4周恢复期的动物中,250毫克/千克剂量组的变化消失,但500毫克/千克剂量组的变化仍然存在。从这些结果可以得出结论,4周的治疗期足以评估药物对雄性生育能力的影响,并且组织病理学可以检测到对睾丸最轻微的毒性作用。