These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Co-metabolism of ethanol, ethanol-derived acetaldehyde, and 4-hydroxynonenal in isolated rat hepatocytes.
    Author: Hartley DP, Petersen DR.
    Journal: Alcohol Clin Exp Res; 1997 Apr; 21(2):298-304. PubMed ID: 9113267.
    Abstract:
    Our laboratory has previously reported on the ability of 4-hydroxynonenal (4-HNE), a primary product of lipid peroxidation, to inhibit acetaldehyde metabolism in isolated mouse liver mitochondria. The purpose of the present study is to determine whether the co-metabolism of ethanol and 4-HNE compromises the elimination of either substrate in isolated rat hepatocytes. Hepatocytes were isolated and incubated with ethanol and 4-HNE. Ethanol elimination and acetaldehyde accumulation were monitored by gas chromatography, whereas 4-HNE elimination and metabolite accumulation were measured by UV detection and reversed-phase HPLC at 202 nm. In the absence of 4-HNE, hepatocytes metabolized ethanol at an initial rate of 9.4 nmol/min/million cells. Ethanol elimination was moderately inhibited by the presence of 4-HNE. Accumulation of ethanol-derived acetaldehyde was not apparent in incubations with only ethanol. In contrast, in incubations containing both substrates, ethanol-derived acetaldehyde accumulation exceeded that observed in hepatocytes exposed only to ethanol and was proportional to the 4-HNE concentration in the incubations. In all instances, the rate of 4-HNE elimination was not compromised by the presence of ethanol. Accordingly, ethanol metabolism did not alter the oxidative or conjugative metabolism of 4-HNE. However, the reductive metabolism of 4-HNE was affected by the presence of ethanol, wherein accumulation of 1,4-dihydroxy-2-nonene increased > 2-fold of that observed in incubations with only 4-HNE. To determine further if 4-HNE and ethanol are metabolized through the same metabolic pathways, cells were preincubated with either 4-methylpyrazole or cyanamide to inhibit alcohol dehydrogenase (E.C. 1.1.1.1.) and aldehyde dehydrogenase (E.C. 1.2.1.2.), respectively. Expectantly, 4-methylpyrazole blocked the formation of 1,4-dihydroxy-2-nonene, but had no effect on the rate of 4-HNE elimination. In contrast, cyanamide substantially inhibited the formation of 4-hydroxy-2-nonenoic acid, decreased the rate of 1,4-dihydroxy-2-nonene formation, but did not decrease the elimination rate of 4-HNE. Overall, these results support our previous observation that 4-HNE inhibits acetaldehyde metabolism and establish that ethanol and 4-HNE are metabolized through the same alcohol dehydrogenase- and aldehyde dehydrogenase-mediated pathways. These data continue to suggest that, as a consequence of enhanced lipid peroxidation resulting from chronic ethanol consumption, increased 4-HNE levels could compromise cellular elimination of ethanol-derived acetaldehyde and thus function in the potentiation of alcoholic liver fibrosis.
    [Abstract] [Full Text] [Related] [New Search]