Authors
Leo MA. Aleynik SI. Aleynik MK. Lieber CS.
Institution
Section of Liver Disease and Nutrition, Bronx Veterans Affairs Medical
Center, NY 10468, USA.
Title
beta-Carotene beadlets
potentiate hepatotoxicity of alcohol [see comments].
Comments
Comment in: Am J Clin Nutr 1997 Dec;66(6):1301-2
Source
American Journal of Clinical Nutrition. 66(6):1461-9, 1997 Dec.
Abstract
Administration of beta-carotene in
beadlets to baboons potentiates alcohol-induced liver
injury. To determine whether this also occurs in other 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 substitution of
ethanol (36% of total energy) for carbohydrates reduced hepatic vitamin A by
80%, and such a depletion was also observed with
beta-carotene as vitamin A precursor. By
contrast, ethanol raised hepatic
beta-carotene, which was further increased
by beadlets. Thus, whereas alcohol promoted hepatic
depletion of vitamin A, it had the opposite effect 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 F2-isoprostanes (measured 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
endoplasmic reticulum and in leakage of the mitochondrial glutamate
dehydrogenase into the plasma, reflecting mitochondrial injury (both
documented by electron microscopy). Thus, in rats given ethanol,
beta-carotene is not an efficient vitamin A
precursor. Its bioavailability was improved by beadlets, but
the ethanol-induced oxidative stress was not attenuated and there was
associated hepatotoxicity that now needs to be assessed in humans.