Combined effect of metformin and gallic acid on inflammation, antioxidant status, endoplasmic reticulum (ER) stress and glucose metabolism in fructose-fed streptozotocin-induced diabetic rats.

Abstract

Over time, diabetes patients usually need combination therapy involving two or more agents, including phytonutrients to attain therapeutic targets. The purpose of this research is to elucidate the combined effect of metformin and gallic acid (GA) on glucose metabolism, inflammation as well as oxidative and endoplasmic reticulum (ER) stresses in fructose-fed diabetic rats. Thirty-five rats of Wistar strain were arbitrarily distributed into five groups, each containing seven animals as follows: normal control, diabetic control, groups administered 100 mg/kg bw metformin only, 50 mg/kg bw gallic acid only and a combination of both. Experimental animals were made diabetic by single injection of 40 mg/kg streptozotocin (intraperitoneally) subsequent to 14 days administration of 10 % fructose prior. Treatment of rats continued for 21 days following diabetes confirmation. Glucose and insulin levels as well as lipid profile were evaluated in the serum, while activities of catalase and superoxide dismutase were estimated in both liver and pancreas. In addition, levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, as well as expression of activating transcription factor-4 were evaluated in liver and pancreas of diabetic rats. Activities of glucose-6-phosphatase and glucokinase were also determined in liver of diabetic animals. Metformin only, GA only and combination of metformin and GA significantly improved antioxidant status and glucose homeostasis while inflammation and endoplasmic reticulum stress were significantly ameliorated in diabetic rats. Metformin/GA combination appeared to improve glucose metabolism by increasing insulin level and ameliorating the dysregulated activities of glucose metabolizing enzymes and ER stress better than either metformin only or GA only. It could be concluded that coadministration of metformin/GA produced a combined effect in ameliorating diabetes in Wistar rats and could be considered in treatment of diabetes.