BETA-CAROTENE BEADLETS POTENTIATE HEPATOTOXICITY OF ALCOHOL

Administration of beta-carotene in beadlets to baboons potentiates alc ohol-induced liver injury. To determine whether this also occurs in ot her species, and whether the beadlet carrier itself contributes to the toxicity, rats were given for 2 mo vitamin A (1.4 U/J), beta-carotene (4.8, 12.0, and 24.0 U/J, with or without beadlets), or corresponding amounts of beadlets without beta-carotene, in diets containing either carbohydrates or equivalent amounts of ethanol. Isoenergetic substitu tion of ethanol (36% of total energy) for carbohydrates reduced hepati c vitamin A by 80%, and such a depletion was also observed with beta-c arotene as vitamin A precursor. By contrast, ethanol raised hepatic be ta-carotene, which was further increased by beadlets. Thus, whereas al cohol promoted hepatic depletion of vitamin A, it had the opposite eff ect on beta-carotene. Ethanol seems to affect the homeostasis of beta- carotene. Furthermore, the ethanol-induced oxidative stress, assessed by an increase in hepatic 4-hydroxynonenal and F-2-isoprostanes (measu red by gas chromatography-mass spectrometry), was not improved despite a concomitant rise in hepatic antioxidants (beta-carotene and vitamin E). Moreover, beadlets resulted in proliferation of the smooth endopl asmic reticulum and in leakage of the mitochondrial glutamate dehydrog enase into the plasma, reflecting mitochondrial injury (both documente d by electron microscopy). Thus, in rats given ethanol, beta-carotene is not an efficient vitamin A precursor. Its bioavailability was impro ved by beadlets, but the ethanol-induced oxidative stress was not atte nuated and there was associated hepatotoxicity that now needs to be as sessed in humans.