Exosome Therapy on Cisplatin-Induced Testicular Tissue Toxicity

Abstract Backround: Cisplatin is a significant chemotherapy drug that has been used for different cancer types. The infertility and gonadotoxicity caused by metabolites resulting from cisplatin metabolism are two of the most serious side effects of cisplatin. Testicular dysfunction is generally caused by oxidative stress and autophagy that are induced by cisplatin. This study focused on potential exosomes' regenerative, antioxidant, and autophagy-regulating properties might be used to minimize testicular damage resulting from cisplatin. Methods For cisplatin toxicity, one dose of 7.5mg/kg was injected on first day. Exosom (80x106/100µl) was injected single dose on sixth day. To examine potential therapeutic effects of the exosome, tissue samples were taken on eighth day. For examination of testicular morphology, tissues were stained with Hematoxylin&Eosin. Sperm motility and number were examined. Autophagy markers and SF-1,StAR expressions, were evaluated immunohistochemistry. Oxidative stress, inhibin and testosterone levels were analysed. Results Cisplatin-induced damage caused to decrease in germinal epithelium, edema in interstitial areas, and degeneration in seminiferous tubules. Sperm motility and quality decreased. When compared to control groups, there was an increase in the expression of Beclin-1, p62, LC3-2, SF-1, and StAR. MDA activity increased,GSH-PX, SOD, and CAT activity decreased. Testosterone and inhibin levels decreased in serum. Tissue morphology was returned to normal, autophagy marker upregulation decreased, and SF-1 and StAR expressions increased in the group that received exosome, following cisplatin. There was a decrease in oxidative stress and increase in hormone levels Conclusion These findings suggest that the exosome may offer a promising approach to minimizing Cis-induced reproductive toxicity and tissue damage by reducing autophagy and improving oxidative stress.