title: Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage.
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.
authors.affiliation: Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Avenida San Rafael Atlixco 186, Colonia Vicentina Iztapalapa, Mexico City, 09340, Mexico.
authors.forename: Blanca Eugenia
authors.initials: BE
authors.lastname: Farfán Labonne
authors.forename: Mario
authors.initials: M
authors.lastname: Gutiérrez
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Gómez-Quiroz
authors.forename: Mina
authors.initials: M
authors.lastname: Konigsberg Fainstein
authors.forename: Leticia
authors.initials: L
authors.lastname: Bucio
authors.forename: Verónica
authors.initials: V
authors.lastname: Souza
authors.forename: Oscar
authors.initials: O
authors.lastname: Flores
authors.forename: Victor
authors.initials: V
authors.lastname: Ortíz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hernández
authors.forename: David
authors.initials: D
authors.lastname: Kershenobich
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Gutiérrez-Ruíz
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology* / Q000633:toxicity*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D000968:Antimycin A; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D005978:Glutathione; D000079:Acetaldehyde; D019803:Glutathione Disulfide