L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits.
This study has been initiated to investigate, in hypercholesterolaemic rabbits, whether L-carnitine deficiency could be an additional risk factor in atherosclerosis, and if so, whether L-carnitine supplementation could prevent the progression of atherosclerosis. Hypercholesterolaemia was induced by feeding rabbits 2% cholesterol-enriched diet for 28 days, whereas, carnitine deficiency was induced by daily i.p. administration of 250 mg kg(-1) of D-carnitine for 28 days. Histopathological examination of aorta and coronaries from hypercholesterolaemic rabbits revealed severe atherosclerotic lesions, intimal plaques and foam cell formation. Also, hypercholesterolaemic diet 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 malonedialdhyde (MDA) levels in aorta and cardiac tissues, respectively. Daily administration 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-carnitine (250 mg kg(-1)) for 28 days increased the progression of atherosclerotic lesions with the appearance of foam cells and apparent intimal plaques which are even larger than that seen in hypercholesterolaemic rabbits. Both L-carnitine and D-carnitine produced similar effects on the lipid profile, GSH and MDA which may point to the conclusion that: (1) L-carnitine prevents the progression of atherosclerotic lesions by another mechanism in addition to its antioxidant and lipid-lowering effects; (2) endogenous carnitine depletion and/or carnitine deficiency should be viewed as an additional risk factor in atherogenesis.
Sayed-Ahmed
M M
MM
Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo, Egypt. mmsayedahmed@hotmail.com
Khattab
M M
MM
Gad
M Z
MZ
Mostafa
N
N
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000473:pathology* / Q000517:prevention & control*; D002331:Carnitine / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D011817:Rabbits; D012307:Risk Factors
D002331:Carnitine