Can troxerutin pretreatment prevent testicular complications in prepubertal diabetic male rats?

OBJECTIVE: The vast majority of type 1 diabetes leads to a higher prevalence of reproductive system's impairments. Troxerutin has attracted much attention owing to its favorable properties, including antihyperglycemic, anti-inflammatory, and antiapoptotic effects. This investigation was proposed to evaluate whether pretreatment with troxerutin could prevent apoptosis-induced testicular disorders in prepubertal diabetic rats. METHODS: Fifty prepubertal male Wistar rats were randomly allocated into five groups: control (C), troxerutin (TX), diabetic (D), diabetic+troxerutin (DTX), and diabetic+insulin (DI). Diabetes was induced by 55 mg/kg of streptozotocin applied intraperitoneally. In TX and DTX groups, 150 mg/kg troxerutin was administered by oral gavage. Diabetic rats in DI group received 2-4 U NPH insulin subcutaneously. Troxerutin and insulin treatments were begun immediately on the day of diabetes confirmation. After 30 days, the testicular lipid peroxidation and antioxidant activity, apoptosis process, and stereology as well as serum glucose and insulin levels were assessed. RESULTS: The results showed that diabetes caused a significant increase in the blood glucose, the number of TUNEL positive cells and tubules, and the malondialdehyde level as well as a significant decrease in serum insulin level compared to controls. The stereological analysis also revealed various alterations in diabetic rats compared to controls. Troxerutin treatment improved these alterations compared to the diabetic group. CONCLUSION: Troxerutin-pretreatment may play an essential role in the management of the type-1 diabetes-induced testicular disorders by decreasing blood glucose and modulating apoptosis.

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.

Voluntary exercise could reduce sperm malformations by improving hypothalamus-hypophysis-gonadal axis and kisspeptin/leptin signaling in type 2 diabetic rats.

Objectives: Most male patients with type 2 diabetes mellitus (T2DM) experience infertility. It is well established that regular physical activity could alleviate diabetic infertility symptoms. This study was designed to determine the effect of voluntary exercise on sperm malformation. Materials and Methods: Thirty-two male Wistar rats were randomly divided into control (C), diabetic (D), voluntary exercise (Ex), and diabetic-voluntary exercise (D-Ex) groups. Diabetes was induced by an intraperitoneal injection of streptozotocin (35 mg/kg) followed by a high-fat diet for four weeks. Voluntary exercise was performed by placing the animals in the rotary wheel cages for ten weeks. Sperm malformations were analyzed. Moreover, the hypothalamic leptin, kisspeptin, kisspeptin receptors (KissR), as well as plasma LH, FSH, testosterone, and leptin levels were evaluated. Results: Results showed that induction of T2DM caused increased sperm malformation, plasma, and hypothalamic leptin as well as decreased hypothalamic kisspeptin, KissR, and plasma LH levels compared with the C group (P<0.001 to P<0.01). Voluntary exercise in the Ex group increased hypothalamic KissR, plasma FSH, LH, and testosterone levels compared with the C group; however, it decreased sperm malformation and hypothalamic leptin levels (P<0.001 to P<0.05). Voluntary exercise in the D-Ex group reduced sperm malformation, hypothalamic leptin, and plasma testosterone while elevated hypothalamic kisspeptin and KissR protein levels compared with the D group (P<0.001 to P<0.01). Conclusion: The results illustrated voluntary exercise reduces sperm malformations by improving the HHG axis and kisspeptin/leptin signaling in rats with T2DM.

Troxerutin affects the male fertility in prepubertal type 1 diabetic male rats.

OBJECTIVES: Diabetes can gradually cause damage to the function and structure of male gonads. This survey was conducted to investigate the effect of troxerutin on hormonal changes, serum oxidative stress indices, and testicular function and structure in prepubertal diabetic rats. MATERIALS AND METHODS: Fifty prepubertal (6 weeks old) male Wistar rats were divided into five groups including Control, Troxerutin, Diabetic, Diabetic+Troxerutin, and Diabetic+Insulin. Type I diabetes was induced by 55 mg/kg of streptozotocin intraperitoneally. The groups were treated with 150 mg/kg/day troxerutin via oral gavage or 4-6 IU/day insulin via subcutaneous injection for 4 consecutive weeks. Blood sugar (BS) and serum levels of insulin, FSH, LH, testosterone, glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC) were analyzed. Testis and epididymis were removed for histopathologic study and analysis of sperm parameters. RESULTS: Troxerutin significantly reduced the BS in the diabetic group similar to insulin but could not affect insulin, FSH, or LH significantly. Troxerutin caused a significant increase in testosterone and GPX but had no significant effect on serum MDA, TAC, and SOD levels. In addition, troxerutin had a better effect than insulin on diabetes-induced testicular structural damage. Sperm analysis results also revealed that troxerutin and insulin could improve sperm number, motility, and viability in diabetic rats. CONCLUSION: According to these results, it can be derived that administration of troxerutin is a suitable protective strategy for side effects of diabetes in testis of prepubertal diabetic male rats.