Abstract

In the present study, the effects of subchronic treatments (4 weeks) of hypercholesterolemic (single) and diabetic-hypercholesterolemic (combined) rats with 4 (3H) quinazolinone and 2 halogenated derivatives (6, 8-dibromo-2-methy-4 (3H) quinazolinone and 6-iodo-2-methyl-4(3H) quinazolinone) at a sublethal dose level (2 mg/Kg) on cholesterol metabolism were investigated. Bezafibrate, a hypolipidemic drug was used as a reference compound for data comparison. Treatment of rats with single and combined hypercholesterolemia with quinazolinone compounds gave rise to highly significant reductions in serum total cholesterol and cholesterol ester levels, whereas serum triacylglycerol level was significantly reduced only after treatment with halogen-substituted quinazolinones in single hyper-cholesterolemia, compared to the control group. The effects of different quinazolinones and bezafibrate on reduction of serum LDL-C level were comparable in single hypercholesterolemia but significantly different in combined hypercholesterolemia. Results obtained from this study suggest that the antihyperlipidemic effect of quinazolinone compounds was brought about by inhibition of dietary cholesterol absorption and / or intestinal ACAT activity.

Highlights

  • Cardiovascular diseases remain by far the number one cause of death for both men and women of all ethnic backgrounds

  • Non significant changes were recorded in the percentage of body weight gain in the treated subgroups at the 4th week point, except for the bezafibrate-treated subgroup, which showed a significant decrease compared to normal controls

  • A parallel reduction in serum triacylglycerol level was noticed in bezafibrate (26.65%), dibromo- (16.83%) and iodoquinazolinone (15.74%) subgroups, compared to the control group

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Summary

Introduction

Cardiovascular diseases remain by far the number one cause of death for both men and women of all ethnic backgrounds. Many causative factors of these diseases are recognized (smoking, high blood pressure, genetic background, diabetes mellitus and obesity) high serum LDL-C and elevated total cholesterol levels are the most prevalent indicators for susceptibility to atherosclerotic heart disease [1,2]. Dyslipidemia, hallmarked by low plasma HDL-C and high LDL-C and triacylglycerol levels, is common in patients with diabetes mellitus. These lipoprotein abnormalities are held to be responsible for considerable cardiovascular disease-related morbidity and mortality [5]. The risk for cardiovascular disease is increased approximately 2 to 4 fold in patients with diabetes mellitus compared with non-diabetic controls [6]

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