The effect of combination therapy with Glibenclamide and Diazepam on Catalase activity in the kidney of Streptozotocin-induced diabetic rats

Background and objective: Diabetes is the leading cause of end-stage renal diseases. Diabetic nephropathy is characterized by pathological changes in the kidney, such as glomerular hypertrophy and renal tubule injury. Such deleterious changes in the diabetic kidney are caused by Increase of oxidative stress and free radicals production in diabetes mellitus. glibenclamide is widely used in treatment of diabetes but it has some adverse effects such as hypoglycemic shock. Diazepam is widely prescribed for the treatment of stress disorders. This study designed to evaluate the effect of combination therapy with glibenclamide and diazepam on catalase enzyme activity of renal tissue in diabetic rats. Materials and methods: In this experimental study, 32 male adult wistar rats ,weighing 200-250 g, were randomly divided into 4 equal groups as follows: diabetic control without treatment, diabetic treated with glibenclamide, diabetic treated with diazepam and diabetic treated with glibenclamide and diazepam. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg). on the third day after injection of streptozotocin, diabetes was verified using glucometer. From the third day after diabetes induction , treated group with glibenclamide get daily 0.3cc, treated group with diazepam get daily 0.2cc and combination therapy group get daily 0.15cc glibenclamide and 0.1cc caffeine by intraperitoneal injection. Two weeks after drug injection the rats anesthesized by ether and after euthanasia, the renal tissue separated. After homogenization and centrifugation, catalase enzyme activity measured with Beer & Sizer method. catalase enzyme activity of renal tissue measured as oxidative stress index with spectrophotometry method. Quantitative data analyzed with one way ANOVA using SPSS. Results: Treatment of diabetic group with glibenclamide significantly enhanced catalase activity versus untreated diabetic rats (p<0.05) and diazepam treatment of diabetic group did not significantly change catalase activity. In addition, treatment of diabetic rats with combination of glibenclamide and diazepam non-significantly increased catalase activity versus diabetic one. Conclusions: It is found out that glibenclamide and not diazepam could restore catalase activity in kidney tissue of diabetic rats and this may be of potential benefit in preventing diabetic nephropathy.

کلیدواژه ها:

Diabetes Mellitus ، Rat ، kidney ، Oxidative Stress ، catalase ، Glibenclamide ، diazepam