Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Afyon Kocatepe, Afyonkarahisar, Turkey.
Department of Anatomy, Faculty of Veterinary Medicine, University of Afyon Kocatepe, Afyonkarahisar, Turkey.
Biomed Pharmacother. 2019 Jan;109:1988-1993. doi: 10.1016/j.biopha.2018.09.139. Epub 2018 Nov 26.
Experimental studies indicate that MK-801 causes organ injury in schizophrenic mice testes although it is molecular mechanism has not been clearly defined. In this study, we investigated the probable protective effect of N-Acetylcysteine (NAC) against MK-801- induced testicular toxicity in mice. In total, 24 Balb/C male mice were divided into 4 equal groups: the animals in the control group (vehicle treated) were intraperitoneally given 10 mL/kg/day saline solution, the animals in the experiment groups were intraperitoneally given 1 mg/kg/day MK-801 alone, 100 mg/kg/day NAC alone and MK-801 by 1 mg/kg/day for 14 days. The level of the testes' total oxidant status (TOS) in mice that were treated with MK-801 was significantly higher than those level in the other groups while the total antioxidant status (TAS) levels decreased. In comparison to the MK-801 group, the TOS levels were lower, and the TAS levels increased in the MK-801 + NAC group. In the morphometric analysis, the diameter and epithelial height of the seminiferous tubules of the testes showed no significant changes after MK-801 administration. Conversely, the weights of the testes decreased significantly. In the treatment with NAC, the weights of testes significantly increased in comparison to the MK-801 group. The histopathological examination revealed necrobiotic and degenerative changes in the epithelial cells, vacuole formation within the seminiferous tubules, a decrease in the number of the spermatozoid, and disorganization in the basement membrane of the seminiferous tubules in the MK-801 group in comparison to the control group. Administration of NAC alleviated several negative effects of MK-801 on the testicular damage in mice. In conclusion, our results showed that NAC protected the mice against the testicular toxicity of MK-801 when it was administrated intraperitoneally.
实验研究表明,MK-801 可导致精神分裂症小鼠睾丸器官损伤,尽管其分子机制尚不清楚。在这项研究中,我们研究了 N-乙酰半胱氨酸(NAC)对 MK-801 诱导的小鼠睾丸毒性的可能保护作用。总共将 24 只 Balb/C 雄性小鼠分为 4 组:对照组(给予 vehicle 处理)小鼠腹腔内给予 10ml/kg/天生理盐水,实验组动物单独腹腔内给予 1mg/kg/天 MK-801、100mg/kg/天 NAC 和 1mg/kg/天 MK-801 共 14 天。与其他组相比,用 MK-801 治疗的小鼠睾丸总氧化状态(TOS)水平明显升高,而总抗氧化状态(TAS)水平降低。与 MK-801 组相比,MK-801+NAC 组 TOS 水平较低,TAS 水平升高。在形态计量学分析中,睾丸曲细精管的直径和上皮高度在给予 MK-801 后没有明显变化。相反,睾丸重量显著下降。在 NAC 治疗中,与 MK-801 组相比,睾丸重量显著增加。组织病理学检查显示,与对照组相比,MK-801 组上皮细胞发生坏死性和退行性变化,曲细精管内形成空泡,精子数量减少,曲细精管基底膜排列紊乱。与 MK-801 组相比,NAC 给药减轻了 MK-801 对小鼠睾丸损伤的几种负面影响。总之,我们的结果表明,NAC 腹腔内给药可保护小鼠免受 MK-801 引起的睾丸毒性。