Metabolic and anti-atherogenic effects of long-term benfluorex in dyslipidemic insulin-resistant sand rats (Psammomys obesus).
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.
Marquié
G
G
Laboratoire de Recherche des Macrophages, Médiateurs de l'Inflammation et Intéractions Cellulaires, Toulouse, France.
El Madani
T
T
Solera
M L
ML
Pieraggi
M T
MT
Hadjiisky
P
P
Ravel
D
D
Seguin
L
L
Bennani
N
N
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000517:prevention & control; D001835:Body Weight / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000009:adverse effects; D005260:Female; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005849:Gerbillinae; D005951:Glucose Tolerance Test; D006949:Hyperlipidemias / Q000209:etiology / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D051381:Rats
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D008055:Lipids; D005277:Fenfluramine; C001584:benfluorex