Beneficial effects of co-administration of PPAR-γ agonist with melatonin on cardiovascular complications associated with diabetes

Abstract

Aim: Effect of PPAR-g agonists, Thiazolidinediones, in combination with melatonin was studied for cardiovascular complications associated with diabetes. Materials and Methods: Diabetic rats were treated with combination of pioglitazone (10 mg/kg/day p.o.) or rosiglitazone (5 mg/kg/day p.o.) with melatonin (10 mg/kg/day p.o.) for 7 weeks. The biochemical parameters, serum glucose, triglyceride, total cholesterol, HDL-cholesterol, AST, LDH and LDL-cholesterol levels were evaluated at the end of 7 weeks. Also cardiovascular parameters like atherogenic index, blood pressure, hisotology of heart were done. Results and Conclusions: The combination treated groups, pioglitazone plus melatonin (PM) and rosiglitazone plus melatonin (RM), showed significant decrease in the blood pressure when compared with diabetic control group. The level of cell injury markers AST and LDH was normalized in the combination groups PM and RM along with significant decrease in the atherogenic index. In the biochemical parameters, the serum glucose, triglyceride, total cholesterol, HDL-cholesterol, and LDL-cholesterol levels were significantly lowered in the combination groups. There was significant inhibition of the myonecrosis, reduction in the infiltration and inflammatory cells, and vacuolar changes when compared with diabetic control. The combination treated groups also proved to be effective in normalizing the levels of SOD, GSH, catalase, and LPO in heart homogenates when compared with diabetic control as well as pioglitazone, rosiglitazone, and melatonin-alone-treated groups. Hence, it may be concluded that the combination of PPAR-g agonists, thiazolidinediones, with melatonin may be beneficial in the treatment of diabetes-induced cardiovascular complications.