Abstract
Acetaldehyde (Ac), the main metabolite of ethanol oxidation, is a very reactive compound involved in alcohol-induced liver damage. In the present work, we studied the effect of Ac in mitochondria functionality. Mitochondria from Wistar rats were isolated and treated with Ac. Ac decreased respiratory control by 50% which was associated with a decrease in adenosine triphosphate content (28.5%). These results suggested that Ac could be inducing changes in cell redox status. We determined protein oxidation, superoxide dismutase (SOD) activity, and glutathione ratio, indicating that Ac induced an enhanced oxidation of proteins and a decrease in SOD activity (90%) and glutathione/oxidized GSH ratio (36%). The data suggested that Ac-induced oxidative stress mediated by mitochondria dysfunction can lead to cell sensitization and to a second oxidative challenge. We pretreated hepatocytes with Ac followed by treatment with antimycin A, and this experiment revealed a noticeable decrease in cell viability, determined by neutral red assay, in comparison with cells treated with Ac alone. Our data demonstrate that Ac impairs mitochondria functionality generating oxidative stress that sensitizes cells to a second damaging signal contributing to the development of alcoholic liver disease.
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Acknowledgments
This work was partially funded by grants from the Consejo Nacional de Ciencia y Tecnología (CONACYT: 45921 and 61544), Secretaría de Educación Pública (PIFI2006-35-129-346/CA 142006-35-40), and the Universidad Autónoma Metropolitana-Iztapalapa.
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Farfán Labonne, B.E., Gutiérrez, M., Gómez-Quiroz, L.E. et al. Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage. Cell Biol Toxicol 25, 599–609 (2009). https://doi.org/10.1007/s10565-008-9115-5
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DOI: https://doi.org/10.1007/s10565-008-9115-5