Effects of liraglutide on the testis in experimental diabetic and ischemia-reperfusion injury

Testicular torsion is an urological condition appeared frequently in adolescents and neonatal periods. The basic pathology of testicular torsion is tissue damage that occurs along with biochemical and morphological changes, following the generation of reactive oxygen species by torsion. Diabetes mellitus is a systemic disease which can cause chronic and acute complications induced by rising in glucose level of the blood as a result of insulin deficiency, insulin resistance or a combination of both. In recent years, liraglutide application has been reported for glycemic control of type 2 diabetic patients specifically. Also experimental studies are reviewed in various organs and tissues such as kidney, heart, stomach, intestine, brain, pancreas, ovary, liver and adipose tissue. However, we found only a few studies about the effects of liraglutide on the male reproductive system in the literature. Therefore, the aim of our study was to investigate the antidiabetic, antioxidative and antiapoptotic effects of liraglutide on the rat testis which were experimentally subjected to diabetes and ischemia/reperfusion injury. In our study, 36 male adult Wistar albino rats were divided into 3 groups: control group (Group 1, n=6), diabetes group (Group 2, n=12), torsion group (Group 3, n=18). Blood glucose levels of rats in group 2 were measured 72 hours after 50 mg/kg streptozocin application and > 300 mg/dl glucose levels were considered as diabetic. Also these diabetic rats were divided into 2 subgroups. Rats in group 2a kept alive for 14 days under normal conditions, while rats in group 2b were administered 0.3 mg/kg liraglutide subcutaneously two times in a day for 14 days. Torsion was created by rotating the left testis 720° in rats of group 3. Then rats in group 3 were divided into 3 subgroups. Rats in group 3a were sacrified 3 hours after torsion. Rats in group 3b were survived for 14 days after detorsion following the 3 hours torsion period. Rats in group 3c were injected 0.3 mg/kg liraglutide subcutaneously at the second hour of torsion, one hour after injection detorsion was created and injection was continued 2 times a day for 14 days. MDA, SOD, and testosterone levels measured from blood samples of sacrified rats. Also testicular tissue samples were examined with using light and electron microscope. Expression of apoptotic marker caspase-3 in testis tissue sections were shown immunohistochemically. In our study, degenerations in seminiferous tubules and edema in the interstitium were observed in the light microscopic examination of diabetes (Group 2a), torsion (Group 3a) and torsion/detorsion (Group 3b) groups. In the ultrastructural examination of these groups; giant lipid droplets, SER vacuolizations and degenarative mitochondria were remarked in the electron dens Sertoli cell cytoplasm. Also shrinkages and apoptotic changes in the spermatogenic cells were shown. On the other hand, in light microscopic examinations, group 2b and group 3c were observed relatively in normal morphology. But in the electron microscopic examination of these groups, anormal spermatids with double nuclei, immature, phagocytic and apoptotic cells were found in the lumen of some seminiferous tubules. While caspase-3 expressions were observed in group 2a, group 3a and group 3b, group 2b and 3c showed similar expressions with the control group. Furthermore, MDA levels of group 2a, group 3a and group 3b were increased, also SOD and testosterone levels were decreased. But in group 2b and group 3c, SOD, MDA and testosterone levels were found similar with the control group. When all the findings were evaluated together, it was thought that positive effects of liraglutide on structural changes and hormon levels in diabetes and torsion/detorsion groups could be more effective with long-term using. It is considered that, in future with further studies and increasing in knowledge about effects of liraglutide on testis, liraglutide can be an alternative therapeutic agent for preserving structure and function of testis in patients with diabetes and cases with torsion/detorsion.