Berberine inhibits experimental varicocele-induced cell cycle arrest via regulating cyclin D1, cdk4 and p21 proteins expression in rat testicles

The aim of this study was to uncover the protective effect of berberine (BBR), an antioxidant chemical, on experimental varicocele (VCL)-induced adverse effects on cell cycle machinery during early germ cells mitosis. To follow-up this study, 30 mature male Wistar rats were divided into control-sham, nontreated VCL, 50mg kg(-1) and 100mg kg(-1) BBR-treated VCL groups. Following 60days, histological alterations were analysed by haematoxylin and eosin (H and E) staining, and expressions of cyclin-D1, cyclin-dependent kinase-4 (cdk4) and p21 were investigated by immunohistochemical (IHC) staining technique. Finally, DNA ladder test was carried out to examine the testicular DNA fragmentation. Administration of BBR remarkably diminished the percentage of seminiferous tubules with deformed shape, depleted germ cells and germ cells dissociation compared to VCL-sole group. The IHC observations showed that BBR significantly (p<.05) reduced VCL-induced p21 expression increase and up-regulated cyclin-D1 and cdk4 expressions. Moreover, BBR decreased VCL-induced DNA fragmentation. In conclusion, BBR can promote cell cycle through cellular DNA content protection, p21 expression down-regulation and maintaining cyclin-D1 and cdk4 expressions. Thus, BBR could be considered as a novel protective biochemical agent against experimental VCL-induced derangements. However, more studies are needed to uncover BBR-induced effects on cells cycle process and germ cells development.