Bone W, Yeung C H, Skupin R, Haufe G, Cooper T G
Institute of Reproductive Medicine, Chemistry of the University, Münster, Germany.
Int J Androl. 1997 Dec;20(6):347-55. doi: 10.1046/j.1365-2605.1998.00077.x.
Ornidazole, a 5-nitro-imidazole derivative, has contraceptive properties in rats. As some ornidazole passes through the body unmetabolized after administration, the aim of this study was to investigate if ornidazole itself has a direct effect on sperm motility and whether these effects are limited or potentiated by the epididymal epithelium or structural changes to the molecule. Cauda epididymal spermatozoa or cauda epididymal tubules were incubated with ornidazole or ornidazole analogues, and motility parameters were subsequently measured by means of a computer-assisted sperm analysis (CASA) system. Incubation of spermatozoa in 2.5 mmol/L ornidazole for 4 h reduced their motility significantly, whereas incubation of epididymal tubules for 8 h in 10 mmol/L ornidazole was required to alter the velocity parameters of the enclosed spermatozoa upon release, suggesting that extratubular non-metabolized ornidazole can participate in inhibiting the motility in vivo. The in vitro toxicity of ornidazole derivatives depends on the halogen present and on the position of the nitro-group. The putatively inactive (R)- and the active (S)-ornidazole exhibited equivalent depression of sperm motility by direct incubation. This observation, and the differences between the in vitro and the in vivo efficacies of various ornidazole analogues, indicates distinct mechanisms of motility inhibition in the two experimental systems.
奥硝唑是一种5-硝基咪唑衍生物，在大鼠中具有避孕特性。由于给药后部分奥硝唑未经代谢就通过人体，本研究的目的是调查奥硝唑本身是否对精子活力有直接影响，以及这些影响是否受到附睾上皮的限制或增强，或者分子结构变化的影响。将附睾尾精子或附睾尾小管与奥硝唑或奥硝唑类似物一起孵育，随后通过计算机辅助精子分析（CASA）系统测量活力参数。在2.5 mmol/L奥硝唑中孵育精子4小时会显著降低其活力，而在10 mmol/L奥硝唑中孵育附睾小管8小时才能改变释放后其中精子的速度参数，这表明管外未代谢的奥硝唑可参与体内抑制活力。奥硝唑衍生物的体外毒性取决于存在的卤素和硝基的位置。推定无活性的（R）-奥硝唑和活性的（S）-奥硝唑通过直接孵育对精子活力的抑制作用相当。这一观察结果以及各种奥硝唑类似物体外和体内功效的差异，表明在两个实验系统中存在不同的活力抑制机制。
