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Alcohol and Alcoholism Vol. 36, No. 4, pp. 281-285, 2001
© 2001 Medical Council on Alcoholism

Toxicity of ß-carotene and its exacerbation by acetaldehyde in HepG2 cells

Ruoyu Ni, Maria Anna Leo, Jingbo Zhao and Charles S. Lieber,*

Liver Disease & Nutrition Section, Veterans Affairs Medical Center & Mount Sinai School of Medicine, Bronx, NY 10468-3992, USA

Received 20 September 2000; in revised form 18 December 2000; accepted 15 January 2001

In rats and baboons, the hepatotoxicity of chronic ethanol consumption is exacerbated by ß-carotene feeding, but the mechanism of this adverse effect is unknown. In this study, the toxicity of ß-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, ß-carotene or acetaldehyde inhibited mitochondrial reduction function as indicated by a decrease of the MTT test. ß-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 ß-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 ß-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 ß-carotene is toxic to hepatocytes, especially when combined with acetaldehyde, the metabolite of ethanol.


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