Dimethyl Fumarate Protects Diabetes-Induced Testicular Toxicity in Rats: Investigations on Nrf-2/HO-1 and β-Catenin/OCT-4 Signalling Pathways

Abstract

Type 1 Diabetes Mellitus (T1DM) is associated with the destruction of insulin-producing β-cells and is characterized by prolonged hyperglycemia. This can increase oxidative stress which eventually damages the male reproductive system, disturbs the production of testosterone, alters semen quality and histological architecture, and increases testicular apoptosis. Dimethyl Fumarate (DMF) is an Nrf-2 activator that has been explored as possible protective agent in several preclinical studies, although its exact role in germ-cell toxicity is still not well-known. In the present study, an attempt has been made to elucidate the role of DMF in testicular toxicity in Sprague-Dawley (SD) rats. Animals having fasting blood glucose >250 mg/dl after treatment with Streptozotocin (STZ; 55 mg/kg, i.p) were considered diabetic. Three doses of DMF (12.5, 25, and 50 mg/kg) were administered to the diabetic animals for 4 consecutive weeks. The testicular damage was characterized by evaluating organ index, biochemical and histological parameters, sperm-related indices, DNA strand breaks, and expression of different proteins. The results revealed that treatment with DMF ameliorated diabetes-induced testicular damage by decreasing testicular oxidative stress and apoptosis, increasing testosterone production, and upregulating the expressions of Nrf-2, HO-1, IL-10, β-Catenin, OCT-4, 3β-HSD, Bcl-2 and downregulating NF-κB, Bax. The present finding suggests that DMF has a protective effect against diabetes-induced testicular damage in SD rat.