Simvastatin Potentiates the Antihyperglycemic, Antidyslipidimic and Antioxidative Effect of Glibenclamide on Alloxan-Induced Diabetic Rats

Abstract

The aim of the current study is to investigate the effect of combination of glibenclamide; an antidiabetic drug and simvastatin; a HMG-CoA reductase inhibitor on long-term (four weeks) alloxan-induced diabetes rats (ADRs). Methods: Alloxan (120 mg/kg body weight, BW) was injected intra-peritonially (i.p.) in rats. At first alloxan (120 mg/kg BW) induced diabetic rats were treated with single dose of glibenclamide (1.2 mg/70kg BW) and simvastatin (10 mg/70kg BW) for two weeks. Then fixed dose combinations of glibenclamide (0.6 mg/70kg BW) and simvastatin (5 mg/70kg BW) were injected along with those of two drugs for four weeks. Results: At first it was found that glibenclamide reduced significant amount of glucose in blood, but it had no significant effect on lipid profile on short term (two weeks) ADRs. In contrast, simvastatin had no effect on blood glucose level, whereas it significantly reduced total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) and increased significant amount of high density lipoprotein cholesterol (HDL-C). However, pathological changes of pancreas’s Islets of Langerhans were observed only after long-term (four weeks) induction of alloxan in rats. The inhibitory effect of combination therapy on blood glucose, TC, TG and LDL-C level was higher than those of monotherapy alone on long term ADRs. In addition, treatment with combination therapy on long term ADRs showed higher amount of HDL-C level and super oxide dismutase and catalase enzyme activity than those with monotherapy. They also decreased serum glutamic pyruvic transaminase (SGPT) and Serum glutamic oxaloacetic transaminase (SGOT) level. Administration of simvastatin recovered Langerhans cells from shrinkage whereas glibenclamide displayed slight recovery. But the combination therapy showed complete recovery of Langerhans cells as compared with diabetic rats. Conclusion: Our present findings suggest that treatment of glibenclamide in combination with simvastatin may be more effective than mono-therapy for preventing diabetes in rats. It may also suggest that this combination may have some beneficial effects on reducing cardiovascular risks from long term diabetes in rats.