Toxicity of beta-carotene and its exacerbation by acetaldehyde in HepG2 cells.
In rats and baboons, the hepatotoxicity of chronic ethanol consumption is exacerbated by beta-carotene feeding, but the mechanism of this adverse effect is unknown. In this study, the toxicity of beta-carotene and acetaldehyde was documented by the MTT test (an assay of reduction of tetrazolium to formazan) and by lactate dehydrogenase (LDH) leakage. In HepG2 cells, beta-carotene or acetaldehyde inhibited mitochondrial reduction function as indicated by a decrease of the MTT test. beta-Carotene was inhibitory at very low concentration, in a dose-dependent manner. The combination of these two compounds resulted in an additive effect. Acetaldehyde increased LDH leakage from the HepG2 cells into the medium, whereas beta-carotene by itself did not show such an effect, but it exacerbated the toxicity of acetaldehyde when combined. In addition, this study showed that acetaldehyde and beta-carotene inhibited each other's clearance from the medium, which suggests that these two chemicals may share, at least in part, a common metabolic pathway (possibly via aldehyde dehydrogenase) in the cells, and that a competitive inhibition may exist. In conclusion, this preliminary study indicates that beta-carotene is toxic to hepatocytes, especially when combined with acetaldehyde, the metabolite of ethanol.
Ni
R
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Liver Disease & Nutrition Section, Veterans Affairs Medical Center & Mount Sinai School of Medicine, Bronx, NY 10468-3992, USA.
Leo
M A
MA
Zhao
J
J
Lieber
C S
CS
D000079:Acetaldehyde / Q000378:metabolism* / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D019207:beta Carotene / Q000494:pharmacology* / Q000633:toxicity*
D019207:beta Carotene; D000431:Ethanol; D000079:Acetaldehyde