ANTIOXIDANT ACTIONS OF BETA-CAROTENE IN LIPOSOMAL AND MICROSOMAL-MEMBRANES - ROLE OF CAROTENOID-MEMBRANE INCORPORATION AND ALPHA-TOCOPHEROL

beta-Carotene and other carotenoids are widely regarded as biological antioxidants. However, recent clinical trials indicate that beta-carot ene supplements are not effective in disease prevention and raise ques tions about the biological significance of carotenoid antioxidant acti ons. To further explore this issue, we have reevaluated the antioxidan t actions of beta-carotene in liposomal and biological membrane system s. In dilinoleoylphosphatidylcholine liposomes in which 0.35 mol % bet a-carotene was incorporated into the bilayer during liposome preparati on, the carotenoid inhibited lipid peroxidation initiated by 10 mM azo bis[amidino-propane HCl] (AAPH). In carotenoid-free liposome suspensio ns to which the same amount of beta-carotene was added, no antioxidant effect was observed. Supplementation of rat liver microsomes with bet a-carotene in vitro yielded microsomes containing 1.7 nmol p-carotene mg(-1) and 0.16 nmol alpha-tocopherol mg(-1) microsomal protein. In be ta-carotene supplemented microsomes incubated with 10 mM AAPH under an air atmosphere, lipid peroxidation did not occur until alpha-tocopher ol was depleted by approximately 60%. beta-Carotene exerted no apparen t antioxidant effect and was not significantly depleted in the incubat ions. Similar results were obtained when the incubation was done at 3. 8 torr O-2. In liver microsomes from Mongolian gerbils fed beta-carote ne-supplemented diets, beta-carotene levels were 16-37% of alpha-tocop herol levels. The kinetics of AAPH-induced lipid peroxidation were no different in beta-carotene-supplemented microsomes than in microsomes from unsupplemented animals, although the kinetics of beta-carotene an d alpha-tocopherol depletion were similar. The results indicate that b eta-carotene is ineffective as an antioxidant when added to preformed lipid bilayer membranes and that alpha-tocopherol is a much more effec tive membrane antioxidant than beta-carotene, regardless of the method of carotenoid-membrane incorporation. These results support a reevalu ation of the proposed antioxidant role for beta-carotene in biological membranes. (C) 1997 Academic Press.