title: Cholesterol Enhances the Toxic Effect of Ethanol and Acetaldehyde in Primary Mouse Hepatocytes.
abstract: Obesity and alcohol consumption are risk factors for hepatic steatosis, and both commonly coexist. Our objective was to evaluate the effect of ethanol and acetaldehyde on primary hepatocytes obtained from mice fed for two days with a high cholesterol (HC) diet. HC hepatocytes increased lipid and cholesterol content. HC diet sensitized hepatocytes to the toxic effect of ethanol and acetaldehyde. Cyp2E1 content increased with HC diet, as well as in those treated with ethanol or acetaldehyde, while the activity of this enzyme determined in microsomes increased in the HC and in all ethanol treated hepatocytes, HC and CW. Oxidized proteins were increased in the HC cultures treated or not with the toxins. Transmission electron microscopy showed endoplasmic reticulum (ER) stress and megamitochondria in hepatocytes treated with ethanol as in HC and the ethanol HC treated hepatocytes. ER stress determined by PERK content was increased in ethanol treated hepatocytes from HC mice and CW. Nuclear translocation of ATF6 was observed in HC hepatocytes treated with ethanol, results that indicate that lipids overload and ethanol treatment favor ER stress. Oxidative stress, ER stress, and mitochondrial damage underlie potential mechanisms for increased damage in steatotic hepatocyte treated with ethanol.
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico.
authors.forename: Anayelly
authors.initials: A
authors.lastname: López-Islas
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico.
authors.forename: Victoria
authors.initials: V
authors.lastname: Chagoya-Hazas
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pérez-Aguilar
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico.
authors.forename: Mayrel
authors.initials: M
authors.lastname: Palestino-Domínguez
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico; Red Fisiopatología de las Enfermedades Hepáticas, PRODEP-SEP, México, DF, Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Souza
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico; Red Fisiopatología de las Enfermedades Hepáticas, PRODEP-SEP, México, DF, Mexico.
authors.forename: Roxana U
authors.initials: RU
authors.lastname: Miranda
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico; Red Fisiopatología de las Enfermedades Hepáticas, PRODEP-SEP, México, DF, Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Bucio
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico; Red Fisiopatología de las Enfermedades Hepáticas, PRODEP-SEP, México, DF, Mexico.
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Gómez-Quiroz
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, 09340 México, DF, Mexico; Red Fisiopatología de las Enfermedades Hepáticas, PRODEP-SEP, México, DF, Mexico.
authors.forename: María-Concepción
authors.initials: MC
authors.lastname: Gutiérrez-Ruiz
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology*; D008055:Lipids / Q000737:chemistry; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D008055:Lipids; D000431:Ethanol; D002784:Cholesterol; D019392:Cytochrome P-450 CYP2E1; D000079:Acetaldehyde