Carvedilol alleviates testicular and spermatological damage induced by cisplatin in rats via modulation of oxidative stress and inflammation

Abstract

The clinical application of the anticancer drug cisplatin is limited by its deleterious side effects, including male reproductive toxicity. In this context, the potential protective effect of carvedilol on testicular and spermatological damage induced by cisplatin in male Sprague–Dawley rats was investigated. Carvedilol was orally administered at a dose of 10 mg/kg for 2 weeks, and cisplatin was given as a single intraperitoneal injection of 10 mg/kg on the 12th day to induce toxicity. Cisplatin significantly reduced reproductive organ weight, sperm count and sperm motility, and increased sperm abnormalities and histopathological damage of testicular tissue. In addition, it resulted in a significant decline in serum testosterone as well as levels of testicular enzymatic and non-enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxides, and reduced glutathione). Moreover, cisplatin remarkably augmented malondialdehyde, nitric oxide, tumor necrosis factor-α, and nuclear factor-kappa B contents in testicular tissue. Conversely, carvedilol administration markedly mitigated cisplatin-induced testicular and spermatological injury as demonstrated by suppression of oxidative/nitrosative and inflammatory burden, amendment of antioxidant defenses, enhancement of steroidogenesis and spermatogenesis, and mitigation of testicular histopathological damage. The current study reveals a promising protective action of carvedilol against cisplatin-induced reproductive toxicity by virtue of its anti-inflammatory and antioxidant properties.

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Acknowledgments

The authors are grateful to Prof. Dr. Bakeir A and Prof. Dr. Ahmed KA (Department of Histology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt) for performing the histopathological and immunohistochemical examinations.

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Correspondence to Noha F. Abdelkader.

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Eid, A.H., Abdelkader, N.F., Abd El-Raouf, O.M. et al. Carvedilol alleviates testicular and spermatological damage induced by cisplatin in rats via modulation of oxidative stress and inflammation. Arch. Pharm. Res. 39, 1693–1702 (2016). https://doi.org/10.1007/s12272-016-0833-6

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Keywords

  • Cisplatin
  • Testicular damage
  • Carvedilol
  • Oxidative stress
  • Inflammation