Grape seed proanthocyanidin extract attenuates varicocele-induced testicular oxidative injury in rats by activating the Nrf2-antioxidant system

The present study investigated whether grape seed proanthocyanidin extract (GSPE) can attenuate varicocele-induced testicular oxidative injury through the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant pathway. A varicocele model in rats was established by partial ligation of the left renal vein. Following 4 weeks of GSPE administration, the decreased sperm count and motility and other pathological changes caused by varicocele were significantly alleviated, as indicated by the results of computer-assisted sperm analysis and hematoxylin and eosin staining. In addition, the decreased antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activity and elevated oxidative stress level were partially reversed by administration of GSPE. Furthermore, the apoptotic level of the testis induced by varicocele was decreased by the GSPE treatment, according to terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Additionally, the expression of apoptosis-related proteins, including B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 and cleaved caspase-3, were also affected by GSPE. GSPE activated Nrf2, which is a key antioxidative transcription factor, with elevation of the downstream factor hemeoxygenase-1. These findings suggest that GSPE can ameliorate abnormal spermatogenesis and testicular injury in varicocele rats, potentially due to its antioxidative activity and ability to activate the Nrf2 pathway.