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Effects of Combination of Carvedilol and Melatonin on Induced Metabolic Syndrome in Rats

Khaled A Abdel Sater and Mohamed Mostafa Ahmed Malak

Background: The prevalence of metabolic syndrome is increasing and it is considered one of the main threats to human health worldwide. Fructose feeding induces hyper-insulinemia, insulin resistance and hyper-triglyceridemia. The main objective of the present study is to evaluate the pharmacological effects of the single and combined administration of carvedilol and melatonin in fructose-induced metabolic syndrome in rats. Methods: Male albino rats were fed a high fructose diet for ten weeks to induce metabolic syndrome. Oral administration of carvedilol (20 mg/kg/day), melatonin (10 mg/kg/day), carvedilol and melatonin (20 mg +10 mg/kg/ day) or vehicle was conducted for six weeks after stopping the high fructose feeding.Indices of systolic blood pressure (SBP), Fasting Blood Glucose (FBG), Fasting Serum Insulin (FSI), serum lipid profiles, serum Nitric Oxide (NO), serum lipid peroxides as well as levels of total antioxidants were determined. Insulin resistance index were calculated from FBG and FSI using HOMA-IR (Homeostasis Model Assessment). Results: A high-fructose diet was associated with hypertension, dyslipidemia, insulin resistance, decreased nitrite and increased of oxidative stress. Carvedilol, melatonin or combination of carvedilol and melatonin was able to reverse features of metabolic syndrome in the six weeks. The intensity of changes produced by melatonin was of greater extent in insulin resistance and lipid profiles than produced by carvedilol but the effect of carvedilol was higher in hypertension. The combination of carvedilol plus melatonin was superior of the others. Conclusion: A combination of both carvedilol (20 mg/kg/ day orally) and melatonin (10 mg/kg/ day orally) for 6 weeks revealed a statistical significant results in comparison to carvedilol (20 mg/kg/ day orally) or melatonin (10 mg/kg/ day orally) alone. A combination of carvedilol and melatonin may give an additive effect better than each of them alone.