Metabolic and anti-atherogenic effects of long-term benfluorex in dyslipidemic insulin-resistant sand rats ( Psammomys obesus)

• Published in: Life sciences (1973) Vol. 63; no. 1; pp. 65 - 76
• Main Authors: Marquié, G., El Madani, T., Solera, M.L., Pieraggi, M.T., Hadjiisky, P., Ravel, D., Seguin, L., Bennani, N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1998
• Subjects: Animal Nutritional Physiological Phenomena; Animals; anti-diabetic agent; Aorta - drug effects; Aorta - pathology; Arteriosclerosis - prevention & control; atherosclerosis; benfluorex; Body Weight - drug effects; Cholesterol, Dietary - adverse effects; dyslipidemia; Female; Fenfluramine - analogs & derivatives; Fenfluramine - pharmacology; Gerbillinae; Glucose Tolerance Test; Hyperlipidemias - etiology; Hyperlipidemias - metabolism; hypolipidemic agent; Hypolipidemic Agents - pharmacology; Insulin Resistance; Lipids - blood; Liver - chemistry; Liver - drug effects; Male; Rats; sand rat; syndrome X; benfluorex; atherosclerosis; sand rat; anti-diabetic agent; syndrome X; hypolipidemic agent; dyslipidemia; insulin resistance
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(98)00237-9

Benfluorex is a clinical lipid-lowering agent with antihyperglycemic properties. The effect of long-term oral treatment (10 mg/kg/day for 7.5 months) on carbohydrate and lipid metabolism and aortic morphology was investigated in 24 insulin-resistant sand rats receiving a standard laboratory diet supplemented with cholesterol (2%). Untreated controls (n = 34) developed impaired glucose tolerance, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia and elevated plasma LDL- and VLDL-cholesterol, positively correlated with the proportion of the thoracic aorta displaying oil red O-positive atherosclerosis; ultrastructural examination showed intimal lipid deposits, foam cells, polymorph infiltrates and fibrosis. Benfluorex-treated animals showed significant decreases in glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and plasma LDL- and VLDL-cholesterol, with no evidence of aortic atheroma. The metabolic benefits of benfluorex may protect against the long-term development of atherosclerosis in the insulin-resistant dyslipidemic syndrome.