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Oxidation of low-density lipoprotein plays a crucial role in the pathogenesis of atherosclerosis, raising the possibility of using antioxidants as an inhibitor of atherosclerosis. However, studies with antioxidants have led to contradictory results. In the present study, we investigated the effect of crocetin, a carotenoid with potent antioxidant activity, on experimental atherosclerosis in rabbits. After 8 weeks of feeding on high lipid diet, rabbits developed severe atherosclerotic lesions in thoracic aortas (P < 0.01), together with a significant elevation of plasma lipids level, thiobarbituric acid reactive substances (TBARS), and oxidized low-density lipoprotein (P < 0.01). In contrast, supplementation with crocetin markedly reduced the progression of atherosclerotic lesions (P < 0.01) and plasma levels of Ox-LDL and TBARS, whereas plasma lipids level remained unchanged. Plasma total antioxidant capacity and superoxide dismutase activity were obviously increased in crocetin-treated rabbits. In vitro studies demonstrated that supplementation with crocetin significantly increased the resistance of LDL to cupric ion-induced oxidation. Regression analysis indicated that atherosclerotic areas correlated positively with plasma level of Ox-LDL and the susceptibility of LDL to in vitro oxidation. These findings suggest that suppression of LDL oxidation by crocetin contributes, at least partly, to the attenuation of atherosclerosis.

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