Carvedilol induces the antiapoptotic proteins Nrf2 and Bcl2 and inhibits cellular apoptosis in aluminum-induced testicular toxicity in male Wistar rats

Abstract

The present study was carried out to explore the protective effect of carvedilol (CARV) on aluminum chloride-induced testicular damage in Westar rats. Forty adult male rats, aged 8 weeks, were randomly divided into 4 groups (10 rats each). Group I (control group) received normal saline; whereas group II animals were supplemented with CARV in a dose of 10 mg/kg/day. Group III received AlCl₃ (30 mg/kg/day) whereas group IV was co-administered CARV and AlCl₃ as the same doses in group II and III respectively. The route of the application was oral gavage for CARV and I.P for AlCl₃ for 20 successive days. Exposure of rats to AlCl₃ for 20 consecutive days resulted in a significant decrease in serum and testicular superoxide dismutase and catalase activities, serum testosterone level, and sperm count and motility; on the other hand, an increase in nitric oxide, malondialdehyde, aluminum, and serum tumor necrosis factor-alpha levels. Furthermore, histopathological changes in the testis exhibited marked testicular damage. In addition, it revealed a significant up-regulation in the level of the expression for the apoptotic marker; Caspase-3, and down-regulation in antiapoptotic marker Bcl₂ and Nrf₂ genes. On the other hand, the co-administration of CARV modulated the biochemical parameters, saved sperm count and motility, and the histopathological findings, also, restored the observed changes in Caspase-3, Bcl₂, and Nrf₂ transcriptional genes. These data suggested that administration of CARV protects against AlCl₃ induced testicular oxidative, inflammatory, and apoptosis damage.

Keywords: Carvedilol; Gene expression; Oxidative stress; TNF-α; Testis.