Effects of hypercholesterolemia on tissue antioxidant status in two species differing in susceptibility to atherosclerosis.

Uncontrolled oxidation has been implicated in the pathogenesis of atherosclerosis. In order to investigate the possible influence of hyperlipidemia on endogenous antioxidant status, the effects of dietary cholesterol supplementation on antioxidant enzymes and in vitro susceptibility to oxidative challenge (as measured by glutathione depletion and lipid peroxidation) were compared in two species exhibiting high and low susceptibilities to atherosclerosis, namely Japanese quail and rat, respectively. Standard diets were supplemented with cholesterol and cholic acid (1.0 and 0.5%, by weight, respectively) and assessments of antioxidant status made in red cells, liver, kidney and heart after 1, 2, 5 and 8 weeks. In contrast to the absence of detectable antioxidant alterations in rats, quail showed complex tissue-dependent changes, including increases (possibly adaptive) in antioxidant enzyme activities (usually first apparent at 2 weeks), enhanced susceptibility to peroxide-induced glutathione depletion (heart, kidney and liver) at 5 weeks and decreased sensitivity to lipid oxidation (heart and liver) at 8 weeks. Our results indicate an association of hyperlipidemia with complex time-dependent alterations in antioxidant components in an atherosclerosis-susceptible species prior to the appearance of visible atherosclerotic lesions. Future studies will focus on alterations in antioxidant components associated with atherosclerotic plaque development.