Sodium Butyrate Attenuates Diabetes-Induced Testicular Dysfunction by Modulating Apoptotic Signaling in Male Wistar Rats

Background: Diabetes in males leads to hyperglycemia-induced oxidative stress and inflammation in the testis, resulting in apoptosis. Diabetes-induced testicular impairment has been linked to the implication with the gut–brain axis. Sodium butyrate, a product of the gut microbiota fermentation process, has been targeted for its anti-diabetic, anti-inflammatory, and antioxidative functions. This research, therefore, explored sodium butyrate as a therapeutic potential intervention in mitigating diabetes-induced testicular dysfunction. Methods: Thirty-five male rats were randomly assigned to five groups after diabetes was confirmed: healthy control (CON), sodium butyrate-treated (SBUT; 200 mg/kg orally), diabetic control (T1DM; 50 mg/kg STZ intraperitoneally), diabetes + sodium butyrate (T1DM + SBUT), and diabetes + insulin (T1DM + INSL, 0.9 I.U/100 g/day). Body weight, testicular weight, glucose homeostasis (fasting blood sugar, oral glucose tolerance, and glycated hemoglobin), lipid profile, testosterone level, sperm analysis, histopathology of the testis, and anti-apoptotic markers (B-cell lymphoma-2 (Bcl-2), Bcl-associated protein X (Bax), and Caspase-3) were all assessed. Results: Along with elevated blood glucose and glycated hemoglobin levels, diabetic rats showed a notable decrease in body weight, testicular mass, gonadosomatic index, sperm count, motility, viability, and normal morphology. Elevated Bax and Caspase-3 expression with reduced Bcl-2 were observed alongside testicular fibrosis, accumulation of collagen, and carbohydrate-rich substances. Sodium butyrate treatment, by downregulating Bax and Caspase-3 and upregulating Bcl-2, conserved testicular histoarchitecture, restored sperm quality, controlled apoptotic signaling, and markedly improved metabolic indices. Conclusions: Sodium butyrate displayed a protective role in the testis in diabetic conditions via the modulation of hyperglycemia-induced apoptosis, identifying this as a potential therapeutic intervention in diabetes-induced testicular dysfunction.