title: Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles.
abstract: 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.
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Rezvanfar
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Rezvanfar
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Shahverdi
authors.forename: Abbas
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Maryam
authors.initials: M
authors.lastname: Baeeri
authors.forename: Azadeh
authors.initials: A
authors.lastname: Mohammadirad
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000818:Animals; D002374:Catalase / Q000097:blood; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage; D005979:Glutathione Peroxidase / Q000097:blood; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D030421:Peroxynitrous Acid / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000494:pharmacology*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects / Q000502:physiology; D013091:Spermatogenesis / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000097:blood; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D002843:Chromatin; D017392:Thiobarbituric Acid Reactive Substances; D030421:Peroxynitrous Acid; D013739:Testosterone; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium; D002945:Cisplatin