Koohsari M, Ahangar N, Mohammadi E, Talebpour Amiri F, Shaki F
Bratisl Lek Listy. 2020;121(6):400-410. doi: 10.4149/BLL_2020_065.
The present study investigated the role of redox balance, inflammation, mitochondrial dysfunction, and apoptosis in Tramadol (Tra)-induced testicular toxicity.
Twenty-four male Wistar rats were randomly divided into either the control group or the groups receiving different doses of Tra (25, 50, and 75 mg/kg/day, i.p.) for 21 successive days. Testicular tissues were collected for oxidative stress, mitochondrial function, sperm assays and histopathological evaluation. Real-time polymerase chain reaction was performed to evaluate the markers of inflammation and apoptosis.
Tra caused a significant reduction in the sperm count, motility and morphology, while it caused a marked increase in oxidative stress parameters. In addition, Tra induced testicular mitochondrial dysfunction due to the collapse of mitochondrial membrane potential and mitochondrial swelling. It also led to the significant inhibition of anti-apoptotic Bcl-2 expression, besides a significant increase in pro-apoptotic Bax expression. There was a significant increase in the level of tumour necrosis factor-α, interlukin-1β and nuclear factor kappa B. Histopathological degenerative changes were observed in the testis after Tra exposure.
The present results suggest that Tra exposure may lead to reproductive toxicity due to the loss of the antioxidant defence system, mitochondrial dysfunction, and activation of inflammatory and apoptotic pathways (Tab. 4, Fig. 5, Ref. 63).
本研究探讨氧化还原平衡、炎症、线粒体功能障碍和细胞凋亡在曲马多（Tra）诱导的睾丸毒性中的作用。
将24只雄性Wistar大鼠随机分为对照组或连续21天接受不同剂量Tra（25、50和75mg/kg/天，腹腔注射）的组。收集睾丸组织进行氧化应激、线粒体功能、精子检测和组织病理学评估。采用实时聚合酶链反应评估炎症和细胞凋亡标志物。
Tra导致精子数量、活力和形态显著降低，同时导致氧化应激参数显著升高。此外，Tra由于线粒体膜电位崩溃和线粒体肿胀而诱导睾丸线粒体功能障碍。它还导致抗凋亡Bcl-2表达显著抑制，同时促凋亡Bax表达显著增加。肿瘤坏死因子-α、白细胞介素-1β和核因子κB水平显著升高。Tra暴露后睾丸出现组织病理学退行性变化。
目前的结果表明，Tra暴露可能由于抗氧化防御系统丧失、线粒体功能障碍以及炎症和凋亡途径激活而导致生殖毒性（表4，图5，参考文献63）。
