当前位置: X-MOL 学术Reprod. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Tadalafil alleviates cisplatin-induced reproductive toxicity through the activation of the Nrf2/HO-1 pathway and the inhibition of oxidative stress and apoptosis in male rats.
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.reprotox.2020.06.015
Basel A Abdel-Wahab 1 , Saad Ahmad Alkahtani 2 , Ehab A M Elagab 3
Affiliation  

Male reproductive toxicity is a well-known adverse effect of cisplatin (CIS), an important antineoplastic agent used to control several types of cancers. Tadalafil (TDF), is a long-acting phosphodiesterase-5 (PDE5) inhibitor commonly used as treatment for erectile dysfunction. The aim of this work was to study the possible protective effect of TDF against CIS-induced testicular toxicity in rats and the possible involvement of Nrf2/HO-1 pathway, which demonstrates antioxidant and inflammatory activities utilizing zinc protoporphyrin-IX (ZnPP) as HO-1 inhibitor. Results revealed that TDF attenuated the CIS-induced disturbances in sperm count and activities, normalized the serum testosterone level, improved the CIS-induced changes in epididymal and testicular weights and restored the normal structure of testicular tissues. In addition, TDF upregulated the gene expression levels of Nrf2 and HO-1 and the activity of HO-1 whereas, it reduced the CIS-induced changes in testicular oxidative stress markers and the levels of inflammatory mediators (TNF-α and iNOS). Furthermore, TDF antagonized the CIS-induced increase in testicular gene expression of apoptotic markers caspase-3 and Bax, and the decrease in Bcl-2. However, ZnPP co-administration significantly attenuated all TDF-mediated improvements in CIS-induced testicular toxicity, biochemical changes, and apoptosis. In conclusion, TDF exerts a protective effect against CIS-induced reproductive toxicity in males, through different mechanisms, besides its inhibitory action to PDE5, possibly mediated by the upregulation of Nrf2/HO-1, along with its antioxidant, anti-inflammatory, and anti-apoptotic effects. Hence, the use of TDF represents a promising therapeutic approach to protect the male reproductive system from the harmful toxic effects of CIS.



中文翻译:

他达拉非通过激活 Nrf2/HO-1 通路和抑制雄性大鼠的氧化应激和细胞凋亡来减轻顺铂诱导的生殖毒性。

男性生殖毒性是众所周知的顺铂 (CIS) 的副作用,顺铂是一种重要的抗肿瘤药物,用于控制多种类型的癌症。他达拉非 (TDF) 是一种长效磷酸二酯酶 5 (PDE5) 抑制剂,常用于治疗勃起功能障碍。这项工作的目的是研究 TDF 对 CIS 诱导的大鼠睾丸毒性的可能保护作用以及 Nrf2/HO-1 通路的可能参与,该通路证明了利用锌原卟啉-IX (ZnPP) 作为 H2O 的抗氧化和炎症活性-1 抑制剂。结果表明,TDF 可减轻 CIS 引起的精子数量和活动障碍,使血清睾酮水平正常化,改善 CIS 引起的附睾和睾丸重量变化,恢复睾丸组织的正常结构。此外,TDF 上调了 Nrf2 和 HO-1 的基因表达水平以及 HO-1 的活性,而它降低了 CIS 诱导的睾丸氧化应激标志物和炎症介质(TNF-α 和 iNOS)水平的变化。此外,TDF 拮抗 CIS 诱导的凋亡标志物 caspase-3 和 Bax 的睾丸基因表达增加,以及 Bcl-2 的减少。然而,ZnPP 共同给药显着减弱了 TDF 介导的 CIS 诱导的睾丸毒性、生化变化和细胞凋亡的所有改善。总之,TDF 除了对 PDE5 的抑制作用外,还通过不同的机制对 CIS 诱导的雄性生殖毒性发挥保护作用,这可能是由 Nrf2/HO-1 的上调及其抗氧化、抗炎和抗凋亡作用。因此,

更新日期:2020-07-06
down
wechat
bug