P-4: Grape Seed Extract Alleviate Male Reproductive Toxicity Caused by Busulfan in Rat Model

Background: The alkylating agent busulfan adversely affects spermatogenesis in mammals and Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment druges then the aim of this study was to investigate the possible protective effects of Grape seed extract with potent antioxidant activity, on busulfan-treated adult male mice. Materials and Methods: In this study 40 adult male rats were randomly divided into 4 groups(n=10 each) consisting of a control and 3 experimental groups. The animals in the control group received dimethyl sulfoxide (DMSO and distilled Water), a solvent, the second group was gavaged with busulfan solution, and 2 test groups received Busulfan and grap seed extract daily orally by gavage. All rats in different groups were sacrificed after 45 days and histological analysis of testis and the cauda epididymal sperm analysis for sperm motility, DNA damage concentration in the cauda epididymis, viability and sperm DNA damage was carried out (p<0.05). Results: The histological results obtained from this study revealed that busulfan induced significant histopatological changes in the testis such as decrease in seminiferous tubules diameter(STD), the percentage of seminiferous tubules with positive tubular differentiation (TDI), repopulation (RI) and spermiogenesis (SPI) indexes (p<0.05) than those animals in Grape seed extract -treated groups and the total number of leydig cells were increased in Grape seed extract -treated groups. The cauda epididymal sperm analysis showed that busulfan caused significant decrease in sperm count, motility, and viability, while abnormal sperms increased as compared to control. These changes were associated with significant increase in DNA damage and chromatin abnormality. Notably administration Grape seed extract caused a considerable recovery in above-mentioned parameters (p<0.05). Conclusion: The results suggest that Grape seed extract as an antioxidant have a possible protective effect against busulfaninduced testicular damages.