The Possible Ameliorative Effect of Empagliflozin on Testicular Toxicity induced by Haloperidol in Adult male Albino Rats.

Background: Haloperidol ( HALO ), a first-generation antipsychotic drug, is utilized globally. It works by antagonizing brain dopamine D2 receptors. HALO may negatively impact several sexual function characteristics. Empagliflozin ( EMPA ) has recently been approved as a class of anti-hyperglycemic drug. EMPA can also alleviate oxidative stress and the release of pro-inflammatory cytokines often caused by hyperglycemia. Therefore, the primary aim of this research was to ascertain whether EMPA could mitigate HALO-induced testicular toxicity. Forty mature male rats from the albino strain were separated into four groups of ten rats. These groups include: Control group, EMPA-treated group, HALO-treated group, and EMPA+HALO treated group. Hormonal levels, inflammatory, and oxidative stress biomarkers were evaluated. Histopathological examination was performed for the testicular tissues. Immunohistochemical evaluation was undertaken to measure the expression of Sirt1 and Beclin1 and the results were compared. Results: Results of this study demonstrated that HALO induced significant reduction in Testosterone, Luteinizing Hormone (LH), and Follicle-Stimulating Hormone (FSH). In addition, to significant increase in levels of inflammatory markers, as well as significant reduction in antioxidant levels. Histological and immunohistochemical examination of testicular tissues from HALO-treated group of rats proved that HALO resulted into significant testicular damage. On the other hand, results proved that co-administration of EMPA and HALO significantly elevated Testosterone, LH, and FSH levels. It also, significantly decreased inflammatory markers’ levels as well as increased antioxidant levels. Not only this, but also significantly improved the histological structure of testicular tissues. Immunohistochemistry revealed improved cellular health and autophagy regulation compared to the HALO group. Conclusion: EMPA restored the disturbed hormonal levels, and balanced oxidative stress biomarkers with rapid improvement in the histopathological condition. EMPA exhibited potent anti-inflammatory effects. This implies that EMPA protects against testicular toxicity caused by HALO.