Amelioration of cyclosporine-induced testicular toxicity by carvedilol and/or alpha-lipoic acid: Role of TGF-β1, the proinflammatory cytokines, Nrf2/HO-1 pathway and apoptosis.
Clin Exp Pharmacol Physiol. 2020 Feb 13. Epub 2020 Feb 13. PMID: 32052493
Ahmed M Kabel
Cyclosporine is an immunosuppressive agent that is used to prevent organ rejection after organ transplantation. Due to the widespread use of this type of surgery, the effect of cyclosporine on reproduction and fertility should have a specific interest. Our aim was to assess the effect of carvedilol and/or alpha-lipoic acid on cyclosporine-inducedtesticular toxicity in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; cyclosporine; cyclosporine + carvedilol; cyclosporine + alpha-lipoic acid; cyclosporine + carboxymethyl cellulose and cyclosporine + carvedilol + alpha-lipoic acid. Food intake, testis weight, testicular functions, serum testosterone, luteinizing hormone and follicle stimulating hormone were measured. Also, testicular tissue 3 β-hydroxysteroid dehydrogenase, 17 β- hydroxysteroid dehydrogenase, paroxonase-1, pro-inflammatory cytokines, transforming growth factor beta-1, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Heme oxygenase-1 (HO-1) content and sperm characteristics were determined. Parts of the testes were subjected to histopathological and electron microscopic examination. Carvedilol/alpha-lipoic acid combination restored the food intake, testicular weight and functions, sperm characteristics, hormonal profile and the antioxidant defenses compared to the use of each of these drugs alone. Also, this combination significantly ameliorated inflammation (p<0.05) and induced significant increase in tissue Nrf2/HO-1 content (p<0.05) and significant improvement of the histopathological and electron microscopic picture (p<0.05) compared to the use of each of these drugs alone. So, carvedilol/alpha-lipoic acid combination might represent a novel therapeutic strategy to ameliorate testicular damage induced by cyclosporine.