L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits

This study has been initiated to investigate, in hypercholesterolaemic rabb its, whether L-carnitine deficiency could be an additional risk factor in a therosclerosis, and if so, whether L-carnitine supplementation could preven t the progression of atherosclerosis. Hypercholesterolaemia was induced by feeding rabbits 2% cholesterol-enriched diet for 28 days, whereas, carnitin e deficiency was induced by daily i.p. administration of 250 mg kg(-1) of D -carnitine for 28 days. Histopathological examination of aorta and coronari es from hypercholesterolaemic rabbits revealed severe atherosclerotic lesio ns, intimal plaques and foam cell formation. Also, hypercholesterolaemic di et resulted in a significant 53 and 43% decrease in reduced glutathion (GSH ) levels and a significant (1.87-fold) and (14.1-fold) increase in malonedi aldhyde (MDA) levels in aorta and cardiac tissues, respectively. Daily admi nistration of L-carnitine (250 mg kg(-1)) for 28 days, completely prevented the progression of atherosclerotic lesions induced by hpercholesterolaemia in both aorta and coronaries. Conversely, daily administration Of D-carnit ine (250 mg kg(-1)) for 28 days increased the progression of atheroscleroti c lesions with the appearance of foam cells and apparent intimal plaques wh ich are even larger than that seen in hypercholesterolaemic rabbits. Both L -carnitine and D-carnitine produced similar effects on the lipid profile, G SH and MDA which may point to the conclusion that: (1) L-carnitine prevents the progression of atherosclerotic lesions by another mechanism in additio n to its antioxidant and lipid-lowering effects; (2) endogenous carnitine d epletion and/or carnitine deficiency should be viewed as an additional risk factor in atherogenesis. (C) 2001 Academic Press.