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,\xa0aged 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\xa0mg/kg/day. Group III received AlCl3 (30\xa0mg/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.