title: beta-Carotene beadlets potentiate hepatotoxicity of alcohol.
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.
authors.affiliation: Section of Liver Disease and Nutrition, Bronx Veterans Affairs Medical Center, NY 10468, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Leo
authors.forename: S I
authors.initials: SI
authors.lastname: Aleynik
authors.forename: M K
authors.initials: MK
authors.lastname: Aleynik
authors.forename: C S
authors.initials: CS
authors.lastname: Lieber
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004032:Diet; D004304:Dosage Forms; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014801:Vitamin A / Q000378:metabolism; D019207:beta Carotene / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D002492:Central Nervous System Depressants; D004304:Dosage Forms; D019207:beta Carotene; D014801:Vitamin A; D000431:Ethanol