Effect of Electroacupuncture and Glibenclamide on Blood Glucose Level and Oxidative Stress Parameters in Streptozotocin-Induced Diabetic Rats and Possible Human Implications

Abstract

Diabetes mellitus is a metabolic disorder with increasing global prevalence. It is characterized by impaired glucose utilization that leads to chronic hyperglycemia which is a result of the body's inability to produce insulin (diabetes type I) or inability to make use of insulin (diabetes type II). Long-term hyperglycemia can cause damage to multiple systems, and microvascular and macrovascular complications lead to myocardial infarction, blindness, stroke and renal failure. Diabetes affected 382 million people globally in 2013, and it is estimated to rise up to 592 million by 2035. In spite of its management, both microvascular and macrovascular complications partly linked to oxidative stress are not efficiently prevented. Glibenclamide was approved on the U. S. market for treatment of diabetes type II in 1984. ATP-sensitive potassium channels (KATP) are widely distributed and present in a number of tissues including muscle, pancreatic beta cells and the brain. Glibenclamide closed KATP channels, which leads to depolarization of the cells and insulin secretion. Acupuncture is also a very significant therapeutic method in the complementary medicine. ST36 (Zusanli), CV4 (Guanyuan) and CV12 (Zhongwan) are several acupoints that have been used for treatment of diabetes. In this study for evaluating the effects of glibenclamide and electroacupuncture, 3 parameters such as malondialdehyde, ferric reducing antioxidant power and thiol will be measured. Malondialdehyde (MDA) is the organic compound and it is a marker for oxidative stress. Antioxidants are compounds that inhibit oxidation. Oxidation is a chemical reaction that can produce free radicals, thereby leading to chain reactions that may damage the cells of organisms. Antioxidants such as FRAP and thiol are useful parameters of assessment of oxidative stress. The aim of this study was to evaluate the effects of Electroacupuncture (EA) plus glibenclamide (G) as a novel therapy on diabetic rats and maybe for human. Fifty-four male Wistar rats were randomly divided to 9 groups: 1 non-diabetic control group and 8 diabetic groups (1 sham control group and 7 experimental groups; D/G 2.5 mg/kg, D/G 5 mg/kg, D/G 10 mg/kg, EA, D/EA/G 2.5 mg/kg, D/EA/G 5 mg/kg, and D/EA/G 10 mg/kg). Diabetes was induced by intraperitoneal injection of streptozotocin with high-fat diet. At the end of course, blood samples were obtained. Combination therapy of EA and glibenclamide 5 mg/kg decreased blood glucose better than single therapies (p<0.05) and showed 41 percent decrease in blood glucose as compared to D/G 5 mg/kg group. Combination of EA and glibenclamide 10 mg/kg showed the best effect for decreasing the malondialdehyde level (p<0.05) and also showed 43 percent decrease in comparison to D/G 10 mg/kg group. Combination of glibenclamide 2.5 mg/kg and EA increased the FRAP level better than other treatment groups (P<0.001) andachieved the ferric reducing antioxidant power level near to normal range. Combination of glibenclamide 10 mg/kg with EA increased the thiol concentration better than other treatment groups (P<0.001) and showed 4 percent increase in thiol concentration as compared to D/G 10 mg/kg group. These findings suggest that EA potentiates the effect of glibenclamide to protect animal model and maybe human against oxidative stress and damage.