The possible ameliorative effect of empagliflozin on testicular toxicity induced by haloperidol in adult male albino rats

Haloperidol (HALO), a widely used first-generation antipsychotic, is known to adversely affect sexual function. It works by antagonizing brain dopamine D2 receptors. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has demonstrated antioxidant and anti-inflammatory properties beyond its primary anti-hyperglycemic role. This study aimed to investigate the potential ameliorative effects of EMPA on HALO-induced testicular toxicity in a rat model. HALO administration resulted in significant reductions in testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), alongside elevated inflammatory markers and decreased antioxidant capacity. These biochemical changes were accompanied by marked histopathological damage to the testicular architecture. Conversely, co-administration of EMPA with HALO was associated with significantly higher LH, FSH and testosterone levels, reduced inflammatory markers’ levels and enhanced antioxidant status compared to the HALO-only group. Furthermore, EMPA-treated rats showed preserved histological structure and improved expression of Sirt1 and Beclin-1, suggesting enhanced regulation of autophagy and cellular homeostasis. In this preclinical model, EMPA demonstrated a protective effect against HALO-induced testicular toxicity by modulating oxidative stress, inflammation, and apoptotic pathways. These findings suggest that EMPA may offer a potential gonado-protective strategy, though further studies are required to elucidate the exact mechanisms and clinical relevance.