Therapeutic effect of sodium alginate on bleomycin, etoposide and cisplatin (BEP)-induced reproductive toxicity by inhibiting nitro-oxidative stress, inflammation and apoptosis

海藻酸钠通过抑制硝基氧化应激、炎症和细胞凋亡对博来霉素、依托泊苷和顺铂 (BEP) 诱导的生殖毒性的治疗作用

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作者:Mojtaba Moradi, Mohammad Arshia Hashemian, Azita Faramarzi, Nader Goodarzi, Amir Hossein Hashemian, Hadi Cheraghi, Cyrus Jalili

Abstract

Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the effects of sodium alginate (NaAL) on testicular toxicity caused by bleomycin, etoposide, and cisplatin (BEP). Rats in group 1 received normal saline, while groups 2 and 3 were treated with 25 and 50 mg/kg of NaAL, respectively. Group 4 was treated with a 21-day cycle of BEP (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin), and groups 5 and 6 received BEP regimen plus 25 and 50 mg/kg of NaAL, respectively. Then, sperm parameters, testosterone levels, testicular histopathology and stereological parameters, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), and the expression of apoptosis-associated genes including Bcl2, Bax, Caspase3, p53, and TNF-α were evaluated. Our findings revealed that NaAL improved sperm parameters, testosterone levels, histopathology, and stereology parameters in BEP-administrated rats. NaAL also improved testis antioxidant status by enhancing TAC and ameliorating MDA and NO. Further, modifications to the expression of Bcl2, Bax, Caspase3, p53, and TNF-α suggested that NaAL alleviated BEP-induced apoptosis and inflammation. Collectively, NaAL protects rats' testes against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, apoptosis, and inflammation.

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