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.