Orlistat /Gemfibrozil Ameliorate Testicular Dysfunction in Streptozotocin-Induced Diabetes in Rats via Targeting VEGF/ NO / Programmed Cell Death Factor 4 Signaling Pathways.

Abstract

One of the complex chronic consequences of diabetes is testicular dysfunction, which is well-known yet still has a murky origin. Objective: With the aim of preventing testicular dysfunction in diabetic rats, we looked into the potential effects of orlistat and gemfibrozil on vascular endothelial growth factor (VEGF) as a marker of angiogenesis, nitric oxide (NO) as an oxidative stress marker, and programmed cell death factor 4 (PDCD4) as an apoptotic marker. Methods: Streptozotocin (STZ, 40 mg/kg/i.p. once) was used to induce diabetes in adult rats, and the treated groups received treatment started one week before induction. Rats were sacrificed three weeks later, and blood samples were obtained for hormonal analysis. Additionally, testicular tissue was examined for testicular oxidative stress, inflammatory markers, and apoptotic markers. Additionally, testicular VEGF and androgen receptors were evaluated, and testicular damage was identified. Results: The results revealed a notable decrease in PDCD4 signaling along with a considerable improvement in inflammatory markers, and oxidative stress status. Conclusion: Our data highlight the significance of VEGF/NO/ PDCD4 signaling pathways in the genesis of testicular dysfunction as a consequence of diabetes mellitus and point to the positive benefits of orlistat and gemfibrozil, either separately or in combination, in reducing testicular damage in diabetic rats.