Effects of Ghrelin on germ cell apoptosis and proinflammatory cytokines production in Ischemia-reperfusion of the rat testis

BACKGROUND: Testicular torsion is a medical emergency that requires surgical intervention to reperfuse the affected testis. Ischemia reperfusion injury is usually associated with proinflammatory cytokine generation and apoptosis of germ cells in the testes. OBJECTIVE: In this study we investigate the effect of ghrelin on the proinflammatory cytokines levels and germ cell apoptosis in testicular ischemia reperfusion. MATERIALS AND METHODS: 45 male rats were selected for the study and randomly divided into 3 groups, each containing 15 rats. Animals in the testicular torsion and ghrelin treated groups were subjected to unilateral 720 counterclockwise testicular torsion for 1 hr and then reperfusion was allowed after detorsion for 4 hr, 1 and 7 days. The ghrelin-treated group received intraperitoneal injection of ghrelin 15min before detorsion. The expression levels of bcl-2-associated X protein and proliferating cell nuclear antigen in testicular tissue in the different groups were detected by immunohistochemical assay and tissue cytokines interleukin-1β, tumor necroses factor-α and interleukin-6 were measured using enzyme-linked immunosorbent assay RESULTS: After being treated by ghrelin, the population of immunoreactive cells against BAX in the spermatocytes on day 7 after reperfusion significantly decreased when compared to tortion/ detortion-saline animals (p=0.024). In contrast, PCNA expression in the spermatocytes and spermatogonia were not significantly different between tortion/ detortion-ghrelin and tortion/ detortion-saline groups on both experimental days. Administration of ghrelin significantly attenuated the testicular tumor necroses factor-α and interleukin-6 levels compared with the untreated animals, but had no significant effect on the level of interleukin-1β. CONCLUSION: Ghrelin offers remarkable anti-inflammatory and anti-apoptotic effects in testicular ischemia reperfusion injury.