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Amelioration of cyclosporine-induced testicular toxicity by carvedilol and/or alpha-lipoic acid: Role of TGF-ß1, the proinflammatory cytokines, Nrf2/HO-1 pathway and apoptosis.
Kabel, Ahmed M; Salama, Samir A; Alghorabi, Amal A; Estfanous, Remon S.
Affiliation
  • Kabel AM; Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia.
  • Salama SA; Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.
  • Alghorabi AA; Biochemistry Division and GTMR Unit, Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, Saudi Arabia.
  • Estfanous RS; Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Clin Exp Pharmacol Physiol ; 47(7): 1169-1181, 2020 07.
Article in En | MEDLINE | ID: mdl-32052493
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-induced testicular toxicity in rats. Sixty male Wistar rats were divided into six 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 ß-hydroxysteroid dehydrogenase, 17 ß- hydroxysteroid dehydrogenase, paroxonase-1, proinflammatory 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. The carvedilol/alpha-lipoic acid combination restored the food intake, testicular weight and functions, sperm characteristics, hormonal profile and the antioxidant defences compared to the use of each of these drugs alone. Also, this combination significantly ameliorated inflammation (P < .05) and induced significant increase in tissue Nrf2/HO-1 content (P < .05) and significant improvement of the histopathological and electron microscopic picture (P < .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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Testis / Thioctic Acid / Cyclosporine / NF-E2-Related Factor 2 / Transforming Growth Factor beta1 / Carvedilol / Heme Oxygenase (Decyclizing) Limits: Animals Language: En Journal: Clin Exp Pharmacol Physiol Year: 2020 Document type: Article Affiliation country: Saudi Arabia Country of publication: Australia

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Testis / Thioctic Acid / Cyclosporine / NF-E2-Related Factor 2 / Transforming Growth Factor beta1 / Carvedilol / Heme Oxygenase (Decyclizing) Limits: Animals Language: En Journal: Clin Exp Pharmacol Physiol Year: 2020 Document type: Article Affiliation country: Saudi Arabia Country of publication: Australia