α-Tocopherol Is Ineffective in Preventing the Decomposition of Preformed Lipid Peroxides and May Promote the Accumulation of Toxic Aldehydes: A Potential Explanation for the Failure of Antioxidants to Affect Human Atherosclerosis

Abstract

The decomposition of peroxidized lipids of low-density lipoprotein (LDL) has been suggested to be involved in atherosclerosis. In this study, an in vitro system with 13-hydroperoxylinoleic acid (13-HPODE) was used to determine the effects of antioxidants on its decomposition. Decomposition of 13-HPODE was not affected by a-tocopherol, several other antioxidants, or antioxidant enzymes. Moreover, the inclusion of a-tocopherol during the decomposition of 13-HPODE resulted in an accumulation of aldehydes. Further oxidation of aldehydes to carboxylic acids by a number of oxidases was prevented by a-tocopherol. Conversely, the formation of carboxylic acids may be conducive to plaque stabilization via immunomodulation, rapid degradation, and by calcium sequestration. Thus, the inhibition of formation of carboxylic acids could be a serious deleterious effect of antioxidant treatment. In contrast, a-keto acids, like pyruvic acid, promoted the conversion of 13-HPODE to 13-hydroxylinoleic acid (13-HODE) by readily undergoing decarboxylation into acetate. These observations suggest that agents that promote the reduction of lipid peroxides into lipid hydroxides could be far more effective in treating cardiovascular diseases as opposed a-tocopherol-like antioxidants that could affect additional steps in the oxidation cascade.

Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading

“…RPMI-1640, FBS, penicillin-streptomycin, 1× PBS, NBD Cholesterol (22- TLC using hexane-diethyl ether-acetic acid (30:6:0.5, v/v/v) solvent system, and visualized with iodine vapors ( 35 ). Bands were identifi ed by comparing with authentic standards, and TLC spots corresponding to cholesterol and CE were analyzed with liquid scintillation counter (MicroBeta2 Plate Counter; PerkinElmer).…”

Role of Oxidized Lipids in Atherosclerosis

“…Supplementation of antioxidant vitamins such as -tocopherol, ascorbic acid and -carotene used alone or in combination had long been considered to be cardio protective. However, controlled clinical trials using antioxidant vitamin supplements to prevent CVD have yielded conflicting results (Raghavamenon et al, 2009). While some secondary prevention interventions have been shown with -tocopherol supplementation alone or in combination with ascorbic acid is reported to reduce CVD risk, other studies have shown no effect oftocopherol supplementation in both primary and secondary prevention.…”

“…In such cases, -tocopherol and similar antioxidants could affect the conversion of aldehydes into carboxylic acids. The latter, are presumed to be nonatherogenic and are easily degraded via fatty-acid degradation pathways (Raghavamenon et al, 2009). Based on these arguments it may be necessary for the scientific community to revisit the topic and investigate in well structured studies the type, dose, duration of the anitoxidants on a well defined population of subjects with various stages of CVD and its associated metabolic disorders such as diabetes, obesity and hyperlipidemia.…”

Antioxidant Complexes and Lipoprotein Metabolism – Experience of Grape Extracts Application Under Metabolic Syndrome and Neurogenic Stress

“…In a number of works a clear correlation between the HL activity and the LDLB content in the blood plasma was demonstrated [19]. It is believed that namely HL activation results in the increased LDLB formation [33].…”

“…Stress was caused by immobilization on the abdomen for 3 hours [19]. Animals were decapitated 3 hours after the immobilization.…”