Melatonin protects rats testes against bleomycin, etoposide, and cisplatin-induced toxicity via mitigating nitro-oxidative stress and apoptosis

Biomedicine & Pharmacotherapy

Cyrus Jalili¹  Azita Faramarzi²  Amir Hossein Hashemian³  Nader Goodarzi⁴  Mojtaba Moradi⁵  Hadi Cheraghi⁶ 

[1] Corresponding author at: Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.;Corresponding author.;Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran;Department of Basic and Pathobiological Sciences, Faculty of Veterinary Medicine, Razi Universtiy, Kermanshah, Iran;Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran;Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran;

关键词: Anti-cancer drugs;    Melatonin;    Testicular toxicity;    Sperm;    Apoptosis;    Oxidative stress;   

DOI  :  

来源: DOAJ

【 摘 要 】

There is growing concern that some cytotoxic regimens for cancer adversely affect spermatogenesis and male fertility. Increasing evidence demonstrated that melatonin has beneficial impacts on reproductive processes; however, whether melatonin can protect against bleomycin, etoposide, and cisplatin (BEP) chemotherapy regimen-induced testicular toxicity, remains obscure. The present study aimed to explore the effect of melatonin on BEP-evoked testicular injury in rats. Adult male Wistar rats (n = 10/group) were intraperitoneally (i.p.) injected with one cycle of 21 days of 0.33 therapeutically relevant dose levels of BEP (.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin) with or without melatonin. At the end of the study, sperm parameters, testosterone level, stereology of testes, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), the expression of apoptosis-associated genes such as Bcl2, Bax, Caspase-3, p53, and TNF-α (Real-time PCR and Immunohistochemistry) were evaluated. Our findings showed that melatonin restored spermatogenesis by improving sperm count, motility, viability, and morphology. Testosterone level, histopathology, and stereology of testes were significantly improved in melatonin-administrated groups. Furthermore, melatonin recovered the oxidative status of the testes through elevating TAC and ameliorating MDA and NO levels. More importantly, melatonin therapy suppressed BEP-evoked apoptosis by modulating Bcl-2, Bax, Caspase-3, p53, and TNF-α expression in testes. In conclusion, melatonin protects the testes against BEP-induced testicular damage by attenuating nitro-oxidative stress, apoptosis, and inflammation, which provides evidence for melatonin as a possible clinical therapy against BEP-associated gonadotoxicity and male sub/infertility.

【 授权许可】

Unknown