Amelioration of Hyperalgesia by Gliclazide and Some Antioxidants in STZ diabetic Animals

1. Amelioration of Hyperalgesia by Gliclazide and Some Antioxidants in STZ diabetic Animals HekmaA. Abd El-Latif * Results The obtained results as follow: Single dose of streptozotocin significantly increased serum glucose level and decreased the reaction time in hot plate method. Gliclazide significantly decreased serum glucose level and increased the reaction time. Similarly N-acetylcysteine and resveratrol significantly decreased serum glucose level and increased the reaction time. Likewise combination of gliclazide with either N-acetylcysteine or resveratrol and serum glucose level and elevated reaction time. Serum glucose level was also significantly reduced in diabetic animals which were allowed to drink zamzam water while the reaction time didn`t significantly altered. Zamzam water and gliclazide significantly reduced serum glucose level and significantly elevated reaction time. Abstract Neuropathy is the most common complication of diabetes mellitus. It is a late finding in type 1 diabetes, but can be an early finding in type 2 diabetes. Streptozotocin (STZ) is one of the most commonly used agents to induce diabetic neuropathy in animal models. A single dose (50mg/kg) of STZ was used to induce type II diabetes in rats. Diabetic rats were classified into 8 groups which have been treated with gliclazide (4.5mg/kg). N-actylcysteine (20 mg/kg), Resveratrol (10mg/kg), combination of gliclazide and N-acetylcysteine, combination of gliclazide and resveratrol, zamzam water, and combination of gliclazide and zamzam water. These groups were compared with diabetic control group as well as 2 normal control ones, one of them rats were allowed to drink zamzam water. At the end of 10 days treatment, hyperalgesia was evaluated using hot plate method. In addition body weight as well as fasting serum glucose level was determined. The obtained results as follow: Single dose of streptozotocin significantly increased serum glucose level and decreased the reaction time in hot plate method. Gliclazide significantly decreased serum glucose level and increased the reaction time. Similarly N-acetylcysteine and resveratrol significantly decreased serum glucose level and increased the reaction time. Likewise combination of gliclazide with either N-acetylcysteine or resveratrol and serum glucose level and elevated reaction time. Serum glucose level was also significantly reduced in diabetic animals which were allowed to drink zamzam water while the reaction time didn`t significantly altered. Zamzam water and gliclazide significantly reduced serum glucose level and significantly elevated reaction time. It could be concluded that STZ induced hyperglycemia associated with neuropathy as manifested by hyperalgesia to thermal stimulus. Gliclazide, N-acetylcysteine and resveratrol ameliorated both hyperglycemia and hyperalgesia. • Conclusion • Streptozotcin-induced hyperglycemia and hyperalgesia may be due to liberation of oxygen free radicals and damage of beta-cell. • The ameliorative effects of gliclazide, N-acetylcysteine and resveratrol on hyperalgesia and allodynia in diabetic rats could be due to controlling hyperglycemia and reducing oxidative stress • This finding suggests a potential usefulness of antioxidants for treating diabetes and provides further support for the implication of oxidative stress in diabetic neuropathy. • Further clinical trials are needed to prove this finding Materials and Methods Diabetes was induced by 50 mg/kg of STZ in rats. Hyperglycemia was tested by One Touch Ultra blood glucose monitoring (LifeScan). Diabetic animals were classified into 8 groups and treated with gliclazide (4.5mg/kg), N-actylecysteine (20 mg/kg), Resveratrol (10mg/kg), combination of gliclazide and N-acetylcysteine, combination of gliclazide and resveratrol, zamzam water, and combination of gliclazide and zamzamwater.These groups were compared with diabetic control group as well as 2 normal control ones, one of them was allowed to drink zamzam water. At the end of 10 days body weight was measured as well as hyperalgesia was evaluated for all groups using hot plate method. In addition fasting serum glucose was determined. Table (7): Effect of 10 days daily dose administration of gliclazide alone or in combination with N-acetylcysteine, reasveratrol or zamzam water on body weight in streptozotocin-induced diabetic male rats. ab • Fig. (1): Effect of gliclazide and N-acetylcysteine alone or in combination on serum glucose level • Fig (3): Effect of gliclazide and zamzam water alone or in combination on serum glucose level • Fig (2): Effect of gliclazide and resveratrol alone or in combination on serum glucose level N.B. Data was expressed as mean ± s.e.m. Statistical analysis was carried out using one way analysis of variance (ANOVA) followed by Tukey-Kramer multiple comparisons test @: Significantly different from the corresponding control value at P <0.05. a: Significantly different from the diabetic control group at P <0.05. b: Significantly different from gliclazide group at P < 0.05. N.B. N=6 rats per group, Data was expressed as mean ± seem. Statistical analysis was carried out using one way analysis of variance (ANOVA) followed by Turkey-Kramer multiple comparisons test a: Significantly different from the normal control group at P <0.05. b: Significantly different from the diabetic control group at P < 0.05. c: Significantly different from gliclazide treated group at P <0.05 Fig (5): Effect of gliclazide and resveratrol alone or in combination on thermal hyperalgesia Fig (4): Effect of gliclazide and N-acetylcysteine alone or in combination on thermal hyperalgesia Fig. (6): Effect of gliclazide and zamzam water alone or in combination on thermal hyperalgesia