尽管是一种有效的抗癌药物,顺铂由于其副作用,适用性有限,如睾丸损伤。因此,降低其毒性是必要的。在这项研究中,一种选择性磷酸二酯酶-3抑制剂,西洛他唑,用于治疗间歇性跛行,检查了其消除顺铂诱导的睾丸毒性的能力。将其改善效果与两种磷酸二酯酶抑制剂进行比较,他达拉非和己酮可可碱.该研究还集中于所提出的保护作用的可能机制。顺铂治疗的大鼠精子数量和运动能力显着下降,血清睾酮,和睾丸谷胱甘肽水平,以及丙二醛的显著升高,总亚硝酸盐水平,和肿瘤坏死因子-α的蛋白表达,核因子-κβ,和caspase-3。这些结果通过明显的睾丸结构恶化得到证实。与此相反,西洛他唑,以剂量依赖的方式,显示了对睾丸毒性的潜在保护,逆转了被破坏的睾丸功能,通过氧化应激的再平衡改善组织学改变,炎症,和凋亡。此外,与他达拉非和己酮可可碱相比,西洛他唑具有更明显的保护作用。总之,西洛他唑通过改变氧化应激改善顺铂诱导的睾丸损伤,炎症,和凋亡途径,为顺铂引起的睾丸损伤提供了有希望的治疗方法。
Despite being a potent anticancer drug, cisplatin has limited applicability due to its adverse effects, such as testicular damage. Consequently, reducing its toxicity becomes necessary. In this study, a selective phosphodiesterase-3 inhibitor, cilostazol, which is used to treat intermittent claudication, was examined for its ability to abrogate cisplatin-induced testicular toxicity. Its ameliorative effect was compared to that of two phosphodiesterase inhibitors, tadalafil and pentoxifylline. The study also focused on the possible mechanisms involved in the proposed protective effect. Cisplatin-treated rats showed a significant decrease in sperm number and motility, serum testosterone, and testicular glutathione levels, as well as a significant elevation in malondialdehyde, total nitrite levels, and the protein expression of tumor necrosis factor-alpha, nuclear factor-kappa β, and caspase-3. These outcomes were confirmed by marked testicular architecture deterioration. Contrary to this, cilostazol, in a dose-dependent manner, showed potential protection against testicular toxicity, reversed the disrupted testicular function, and improved histological alterations through rebalancing of oxidative stress, inflammation, and apoptosis. In addition, cilostazol exerted a more pronounced protective effect in comparison to tadalafil and pentoxifylline. In conclusion, cilostazol ameliorates cisplatin-induced testicular impairment through alteration of oxidative stress, inflammation, and apoptotic pathways, offering a promising treatment for cisplatin-induced testicular damage.