Zinc/alogliptin combination attenuates testicular toxicity induced by doxorubicin in rats: Role of oxidative stress, apoptosis and TGF-β1/NF-κB signaling

Abstract

The aim of this study was to assess the effect of alogliptin and/or zinc on doxorubicin (DOX)-induced testicular toxicity in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; DOX; DOX+Zinc; DOX+Alogliptin; DOX+Carboxymethyl cellulose and DOX+Zinc+Alogliptin. Testis weight, testicular functions, serum testosterone, luteinizing hormone, follicle stimulating hormone and zinc were measured. Also, testicular tissue zinc, 3 β-hydroxysteroid dehydrogenase, 17 β- hydroxysteroid dehydrogenase, antioxidant enzymes, pro-inflammatory cytokines, transforming growth factor beta 1 (TGF-β1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and sperm characteristics were assessed. Parts of the testes were subjected to histopathological and immunohistochemical examination. Zinc/alogliptin combination restored the testicular weight and functions, sperm characteristics, serum and tissue zinc levels, hormonal profile and the antioxidant defenses compared to the use of each of these drugs alone. Also, this combination induced significant amelioration of the inflammatory processes, significant increase in tissue Nrf2 content and significant improvement of the histopathological and immunohistochemical picture compared to the use of each of these drugs alone. So, zinc/alogliptin combination might represent a promising therapeutic modality for amelioration of DOX-induced testicular toxicity.

Keywords: Alogliptin; Doxorubicin; Rats; Testis; Zinc sulphate.