Ameliorating diabetes-induced testicular dysfunction by modulating PKC/Nrf2/Bcl-2 signaling: Protective role of sulbutiamine

Abstract

The prevalence of testicular dysfunction is increasing as it is a common diabetes mellites (DM) complication. The objective of this study is to explore the potential protective effect of sulbutiamine against testicular hypofunction associated with streptozotocin (STZ)-induced DM in rats. Sulbutiamine was administered orally (60 mg/kg) to male Wistar rats for 8 weeks starting 72 h after a single injection of STZ (45 mg/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid-derived 2-like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B-cell lymphoma protein 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and caspase-3. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl-2, decreased Bax and reduced caspase-3. The present work revealed for the first time a promising protective role of sulbutiamine against STZ-induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis.