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Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles
Mohammad Amin Rezvanfar1, Mohammad Ali Rezvanfar, Ahmad Reza Shahverdi
1Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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.
Insights
Selenium nanoparticles (Nano-Se) protect against cisplatin-induced male reproductive toxicity by reducing oxidative stress and improving sperm quality. This antioxidant effect helps preserve testicular function and sperm DNA integrity against chemotherapy damage.
Area of Science:
- Reproductive Toxicology
- Nanomedicine
- Biochemistry
Background:
- Cisplatin (CIS), a chemotherapy agent, causes male reproductive toxicity by inducing DNA damage and oxidative stress.
- Selenium nanoparticles (Nano-Se) are potent antioxidants with enhanced bioavailability and reduced toxicity.
- Understanding the protective mechanisms of Nano-Se against CIS-induced gonadotoxicity is crucial for mitigating side effects.
Purpose of the Study:
- To investigate the protective effects of selenium nanoparticles (Nano-Se) against cisplatin (CIS)-induced male reproductive toxicity.
- To elucidate the cellular and biochemical mechanisms underlying this protective effect, focusing on oxidative stress markers.
- To assess the impact on sperm characteristics, DNA integrity, chromatin quality, and spermatogenic disorders.
Main Methods:
- Thirty-two male Wistar rats were divided into four groups: control, CIS-treated, Nano-Se-treated, and combined CIS + Nano-Se.
- CIS (7 mg/kg) and Nano-Se (2 mg/kg/day) were administered via intraperitoneal injection.
- Evaluated sperm parameters, DNA integrity, chromatin quality, lipid peroxidation (LPO), antioxidant enzymes (SOD, CAT, GSH-Px), peroxynitrite (ONOO), and testosterone (T) levels.
Main Results:
- CIS exposure significantly increased LPO and ONOO levels, decreased antioxidant enzyme activity, and reduced serum T concentration.
- CIS treatment led to impaired sperm quality, increased DNA damage, poor chromatin quality, and histological testicular damage.
- Coadministration of Nano-Se significantly improved serum T levels, sperm quality, spermatogenesis, and reduced CIS-induced oxidative stress and DNA damage.
Conclusions:
- Selenium nanoparticles (Nano-Se) demonstrate significant protective effects against cisplatin-induced gonadotoxicity in male rats.
- The protective mechanism involves mitigating oxidative and nitrosative stress through antioxidant properties.
- Nano-Se holds potential as a therapeutic agent to prevent or reduce chemotherapy-induced male reproductive side effects.
