Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Toxicol Appl Pharmacol. 2013 Feb 1;266(3):356-65. doi: 10.1016/j.taap.2012.11.025. Epub 2012 Dec 19.
Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential.
顺铂（CIS）是一种抗癌烷化剂，可诱导 DNA 加合物，并有效地交联 DNA 链，因此作为一种男性生殖毒性剂影响精子。本研究通过评估精子特征、精子 DNA 完整性、染色质质量和精子发生障碍，研究硒纳米粒子（Nano-Se）作为一种已确立的强抗氧化剂，具有更高的生物利用度和更低的毒性，对 CIS 生殖毒性的潜在保护作用的细胞/生化机制。为了确定氧化应激（OS）在 CIS 性腺毒性发病机制中的作用，测量了血液和睾丸中的脂质过氧化（LPO）水平、抗氧化酶，包括超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）以及过氧亚硝酸盐（ONOO）作为硝化应激（NS）的标志物和睾丸功能的生物标志物睾丸酮（T）浓度。32 只雄性 Wistar 大鼠被平均分为四组。单独或联合给予单次 IP 顺铂（7mg/kg）和保护剂量的 Nano-Se（2mg/kg/天）。暴露于 CIS 的大鼠睾丸和血清中的 LPO 和 ONOO 水平显著升高，同时酶抗氧化剂水平显著降低，血清 T 浓度降低，组织学异常，精子质量受损，与 DNA 损伤增加和染色质质量下降相关。Nano-Se 的共同给药显著改善了血清 T、精子质量和精子发生，并减少了 CIS 诱导的自由基毒性应激和精子 DNA 损伤。总之，本研究表明，Nano-Se 可能通过其抗氧化潜力有助于预防 CIS 诱导的性腺毒性。
