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Effect of Nicorandil: A Potassium Channel Opener against Experimentally-induced Hyperlipidemia

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Author(s): D.M. Rathod | H.G. Dodiya | S.S. Goswami

Journal: International Journal of Pharmacology
ISSN 1811-7775

Volume: 7;
Issue: 6;
Start page: 690;
Date: 2011;
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Keywords: nicorandil | antioxidants | atorvastatin | Hypercholesterolemia | lipid peroxidation

ABSTRACT
Hypercholesterolemia often occurs in conjunction with other metabolic risk factors including glucose intolerance, obesity, diabetes and metabolic syndromes. Nicorandil is a potassium channel opener and Nitric Oxide (NO) donor. The aim of study was to evaluate pharmacological effect of nicorandil (2 mg kg-1, orally) on different lipid levels, enzyme-hydroxymethylglutaryl Coenzyme A (HMG-CoA) reductase and antioxidant enzymes. The lipid parameters, HMG-CoA reductase activity and antioxidant enzymes were evaluated in poloxamer-407 (acute model) and high-cholesterol diet-induced hyperlipidemia (chronic model) in Sprague dawley rats. The animals were divided into four groups viz., normal, high cholesterol diet (control), atorvastatin and nicorandil treated animals. In poloxamer-407-induced acute hyperlipidemia model, blood samples were collected at 15 and 24 h period. In high-fat diet-induced model, animals were given respective treatment for the period of twenty one days. Lipid parameters were commonly measured in both the models and compared with reference standard (atorvastatin; 50 mg kg-1). In high fat diet model, antioxidant parameters were additionally measured in the terms of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). High cholesterol diet and poloxamer-407 caused a significant increase in lipid parameters in rats. Nicorandil pre-treatment showed a significant decrease in total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoproteins-cholestero l(VLDL-C) and atherogenic index (AI) in both the models. The results were comparable with that of atorvastatin treated animals. Further, nicorandil showed significant decrease in MDA and SOD along with significant increase in GSH and CAT against high-fat diet model. Based on our data, it is suggested that nicorandil possess hypolipidemic activity. The mechanism of action of this antihyperlipidemic activity of nicorandil could be attributed to its releasing nitric oxide property and inhibit oxidative stress.

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