Protective effects of sodium nitrate against testicular apoptosis and spermatogenesis impairments in streptozotocin-induced diabetic male rats.

Aims: As nitric oxide (NO) production is essential for insulin signaling, glucose uptake, endothelial function, and regulation of apoptosis, the loss of bioavailable NO may be a mechanism underlying the development of diabetes complication. Dietary nitrate acts as a substrate for NO generation, thus serving as a physiological source of NO. This study evaluated the therapeutic effects of nitrate supplementation on the apoptosis-induced testicular disorders in diabetic rats.

Main Methods: Fifty male Wistar rats were divided into five groups; control, control with 100 mg/L nitrate in distilled drinking water, diabetes, diabetes treated with 2-4 U/day NPH insulin, diabetes treated with 100 mg/L nitrate in distilled drinking water. After 8 weeks, blood samples, testis, and epididymis were collected to assess the apoptosis process and the stereology of testis tissue, sperm motility, morphology and DNA fragmentation, and also mRNA expression of miR-449a, p53, Pdcd4, and Pacs2 mRNA, as well as serum glucose, insulin, and NOx levels were investigated.

Key Findings: The results of this study indicated that nitrate treatment ameliorated the sperm parameters, testicular morphometrical and stereological alterations, reduced blood glucose, the number of TUNEL positive cells and tubules, and testicular expressions of p53, Pdcd4, and Pacs2 mRNA as well as increased body weight, serum insulin and NOx levels, and testicular expression of miR-449a in streptozotocin-induced diabetic rats.

Significance: Our in vivo evidence revealed that nitrate treatment may has a favorable effect as an exogenous NO donor on experimental diabetic testicular damages in which NO bioavailability is impaired.