Cisplatin is an effective anticancer used widely in treatment of solid and germ cell tumors, however, the immense toxicity on healthy tissues discourages cisplatin use in prolonged treatment protocols. Testicular toxicity is amongst its undesired adverse effects. Nilotinib is a second generation multityrosine kinase inhibitor which is used as an anticancer agent with anti-inflammatory and antioxidant activities. In the present study, a single dose of cisplatin (7 mg/kg, I.P) to rats induced a significant testicular injury. Daily administration of nilotinib (20 mg/kg, orally) 24 h post cisplatin injection for 10 days ameliorated testicular damage. Nilotinib significantly increased serum testosterone and sperm concentration outside frame of oligospermia with simultaneous full recovery of sperm viability. Nevertheless, biomarkers of apoptosis such as JNKs and Caspase -3, were significantly reduced. Moreover, improved antioxidant status of the testes was inferred by significant elevation of GSR, SOD and TAC alongside with reduction in lipid peroxidation biomarkers; MDA and 4-HNE. Flow Cytometry analysis of the cell cycle confirmed a significant increase in the percentage of testicular cells present in G2/M phase and a significant decrease in the percentage of apoptotic testicular cells after nilotinib administration. Histopathologically, nilotinib preserved testicular architecture showing significant numbers of sperm and spermatids within lumens of seminiferous tubule. Furthermore, nilotinib enhanced testicular expression of Ki67 significantly, providing evidence of testicular regeneration. In conclusion, nilotinib refinement of cisplatin induced testicular toxicity is attributed to enhancing antioxidant capabilities, decreasing apoptotic signals and restoring regenerative capacity of testes suggesting nilotinib to be used in conjunction with cisplatin in treatment protocols to avoid cisplatin induced long term testicular toxicity.

顺铂是一种有效的抗癌药物，广泛用于治疗实体瘤和生殖细胞肿瘤，但是，对健康组织的巨大毒性阻碍了顺铂在长期治疗方案中的使用。睾丸毒性是其不良副作用之一。尼罗替尼是第二代多酪氨酸激酶抑制剂，用作具有抗炎和抗氧化活性的抗癌剂。在本研究中，对大鼠单剂量顺铂（7 mg/kg，IP）会引起明显的睾丸损伤。顺铂注射后 24 小时每日服用尼罗替尼（20 mg/kg，口服），持续 10 天可改善睾丸损伤。尼罗替尼显着增加了少精子症框架外的血清睾酮和精子浓度，同时精子活力完全恢复。尽管如此，凋亡的生物标志物如 JNK 和 Caspase -3 显着减少。此外，通过显着升高 GSR、SOD 和 TAC 以及减少脂质过氧化生物标志物，可以推断出睾丸的抗氧化状态得到改善；MDA 和 4-HNE。细胞周期的流式细胞术分析证实，在尼罗替尼给药后，存在于 G2/M 期的睾丸细胞百分比显着增加，凋亡睾丸细胞百分比显着降低。组织病理学上，尼罗替尼保留了睾丸结构，显示生精小管腔内有大量精子和精子细胞。此外，尼罗替尼显着增强了 Ki67 的睾丸表达，为睾丸再生提供了证据。综上所述，