Evaluation of ameliorative effect of sodium nitrate in experimental model of streptozotocin-induced diabetic neuropathy in male rats.

OBJECTIVE: Diabetes induces sensory symptoms of neuropathy as positive (hyperalgesia), negative (hypoalgesia), or both. METHODS: In the present study, fifty male Wistar rats were allocated to five groups: control, control+nitrate, diabetes, diabetes+insulin, and diabetes+nitrate. Thirty days after diabetes confirmation, insulin (2-4 U/day) was injected subcutaneously in diabetes+insulin group and nitrate (100 mg/l) was added into drinking water of the control+nitrate and diabetes+nitrate groups for a period of 2 months. In order to assess the mechanical and thermal algesia, tail immersion, hot plate, and von Frey tests were performed. The serum insulin levels were determined with insulin ELISA Kit. Serum level of NOx was determined by the Griess method. RESULTS: Both thermal and mechanical nociceptive thresholds showed a significant decrease (p<0.05) which was followed by a significant increase (p<0.01) in the thermal nociceptive threshold in the diabetes group. Chronic nitrate or insulin treatment led to a significant decrease (p<0.01) in blood glucose levels, as well as a significant (p<0.05) increase in the body weight and serum NOx. Moreover, nitrate treatment significantly increased serum insulin levels (p<0.001) compared to the other groups. CONCLUSION: Chronic nitrate treatment modified the thermal and mechanical sensitivities in diabetic animals.

Beneficial treatment effects of dietary nitrate supplementation on testicular injury in streptozotocin-induced diabetic male rats.

RESEARCH QUESTION: Do low doses of dietary nitrate help to attenuate the progression of diabetic reproductive disorders in streptozotocin-induced diabetic male rats? DESIGN: Fifty male Wistar rats were divided into five groups: controls receiving distilled water; controls receiving 100 mg/l nitrate in distilled water; diabetic rats receiving distilled water; diabetic rats receiving insulin 2-4 U/day of neutral protamine hagedorn insulin; and diabetic rats receiving 100 mg/l nitrate in distilled water. Diabetes was induced by 45 mg/kg streptozotocin. Nitrate and insulin treatment were started 4 weeks after diabetes induction for 8 weeks. Serum insulin, nitrogen oxide, stereology of testis, apoptosis, sperm parameters, and mRNA expression of Pdcd4, Pacs2, p53 and miR-449a were assessed at the end of the study. RESULTS: Blood glucose, apoptotic index of seminiferous tubules and expression of p53, Pdcd4, and Pacs2 mRNA were significantly higher in the diabetic rats (P < 0.001). Decreased body weight, serum insulin and nitrogen oxide level, and miR-449a were observed in the diabetic group (P < 0.01 for insulin; P < 0.001 for others). Most sperm parameters and stereological results differed between diabetic and control rats; nitrate recovered almost all these alterations, including dead spermatozoa, sperm motility grade, sperm deformity index, spermatozoa with damaged DNA, malformations in abnormal spermatozoa, total volume of seminiferous tubule, germinal epithelium, capsule, lumen, interstitial tissue, seminiferous tubule diameter, germinal epithelium height, the number of spermatogenic, Sertoli and Leydig cells. CONCLUSIONS: Treatment with sodium nitrate could modulate apoptosis, which is a major cause of diabetic testicular disorder. These experiments suggest that nitric oxide plays an important role in the function of the reproductive system.