Additive effect of lipid lowering drug (simvastatin) in combination with antidiabetic drug (glibenclamide) on alloxan induced diabetic rats with long term dyslipidemia.

Abstract

High blood glucose level, elevated level of liver enzyme, necrosis and shrinkage of islets of Langerhans has been implicated in the pathogenesis of type 2 diabetes. High blood glucose cause oxidative stress, production of free radical as well as elevated SGPT and SGOT level. Both glibenclamide and simvastatin in fixed dose used as antihyperglycemic antidyslipidemic and antioxidative agents for type 2 diabetes treatment. This study therefore aimed to evaluate the antihyperglycemic, antidyslipidemic and antioxidative effect of fixed dose combination of glibenclamide (0.6mg/70kg body weight) and simvastatin (5mg/70kg body weight) on long term alloxan induced diabetic rats with cardiovascular disease using various diagnostic kits as a parameter of phamacotherapeutic and pharmacological effect. The study was carried out using 96 Swiss Albino male rats weighing about 200-220g. Combination therapy induced a significant decrease in blood glucose level in alloxan induced diabetic rats, from 33.75±1.65 to 5.80±0.07mmol/l 2h after last dose administration, after 4weeks treatment. In case of dyslipidemic effect, combination therapy reduced total cholesterol (45%), triglyceride (36%) and low density lipoprotein-cholesterol (32%) levels significantly and increased high density lipoprotein-cholesterol level (57%) in comparison with their respective diabetic control groups. Results of this study showed that combination therapy effectively decreased SGPT (ALAT) (55%) and SGOT (ASAT) (51%) in comparison with diabetic control group. It was also observed that catalase and superoxide dismutase enzyme activity was increased by 58 and 91% respectively in comparison with diabetic control group after 4weeks treatment with combination of both drugs. In conclusion, these findings of combination therapy (glibenclamide and simvastatin) on alloxan induced diabetes in rats are significantly better than monotherapy using single drug. The results of the present study suggest that, combination of the fixed dose of glibenclamide and simvastatin might be efficacious in patients with diabetic dyslipidemia and increased oxidative stress. Furthermore, this combination therapy offer dosage convenience to the patients and by virtue of its dual mode of action might be a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidemia and oxidative stress.