Abstract
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 on 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 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.