title: Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice.
abstract: Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.
authors.affiliation: Postgraduate Program in Experimental Biology, DCBS, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Translational Research Unit, Medica Sur Clinic and Foundation, 14050 Mexico City, DF, Mexico.
authors.forename: Natalia
authors.initials: N
authors.lastname: Nuño-Lámbarri
authors.affiliation: Postgraduate Program in Experimental Biology, DCBS, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico.
authors.forename: Mayra
authors.initials: M
authors.lastname: Domínguez-Pérez
authors.affiliation: Department of Cell Death and Proliferation, Instituto Investigaciones Biomédicas de Barcelona, CSIC, Barcelona and Liver Unit-Hospital Clinic-IDIBAPS and Centro de Investigación Biomédica en Red (CIBERehd), 08036 Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Baulies-Domenech
authors.affiliation: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, Centro de Investigación Biomédica en Red (CIBERehd), Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Monte
authors.affiliation: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, Centro de Investigación Biomédica en Red (CIBERehd), Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.
authors.forename: Jose J G
authors.initials: JJ
authors.lastname: Marin
authors.affiliation: Postgraduate Program in Experimental Biology, DCBS, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rosales-Cruz
authors.affiliation: Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Red "Fisiopatología de Enfermedades Hepáticas" PRODEP-SEP, 09340 Mexico City, DF, Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Souza
authors.affiliation: Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Red "Fisiopatología de Enfermedades Hepáticas" PRODEP-SEP, 09340 Mexico City, DF, Mexico.
authors.forename: Roxana U
authors.initials: RU
authors.lastname: Miranda
authors.affiliation: Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Red "Fisiopatología de Enfermedades Hepáticas" PRODEP-SEP, 09340 Mexico City, DF, Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Bucio
authors.affiliation: General Surgery Service 304, General Hospital of Mexico, UNAM School of Medicine, 06726 Mexico City, DF, Mexico.
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Montalvo-Jave
authors.affiliation: Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Red "Fisiopatología de Enfermedades Hepáticas" PRODEP-SEP, 09340 Mexico City, DF, Mexico.
authors.forename: María
authors.initials: M
authors.lastname: Concepción Gutiérrez-Ruiz
authors.affiliation: Department of Cell Death and Proliferation, Instituto Investigaciones Biomédicas de Barcelona, CSIC, Barcelona and Liver Unit-Hospital Clinic-IDIBAPS and Centro de Investigación Biomédica en Red (CIBERehd), 08036 Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Ruiz
authors.affiliation: Department of Cell Death and Proliferation, Instituto Investigaciones Biomédicas de Barcelona, CSIC, Barcelona and Liver Unit-Hospital Clinic-IDIBAPS and Centro de Investigación Biomédica en Red (CIBERehd), 08036 Barcelona, Spain; Research Center for Alcohol Liver and Pancreatic Diseases and Cirrhosis, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: José C
authors.identifier: 0000-0003-2278-7724
authors.initials: JC
authors.lastname: Fernández-Checa
authors.affiliation: Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico; Red "Fisiopatología de Enfermedades Hepáticas" PRODEP-SEP, 09340 Mexico City, DF, Mexico.
authors.forename: Luis Enrique
authors.identifier: 0000-0002-5704-5985
authors.initials: LE
authors.lastname: Gomez-Quiroz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001652:Bile Ducts / Q000601:surgery; D001663:Bilirubin / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D002779:Cholestasis / Q000209:etiology* / Q000473:pathology; D002784:Cholesterol / Q000032:analysis; D002791:Cholesterol, Dietary / Q000633:toxicity*; D005234:Fatty Liver / Q000209:etiology; D005978:Glutathione / Q000032:analysis; D007150:Immunohistochemistry; D007565:Jaundice / Q000209:etiology; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008111:Liver Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D061213:Mortality, Premature; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014280:Triglycerides / Q000032:analysis
chemical_list: D002791:Cholesterol, Dietary; D019394:Ki-67 Antigen; D017382:Reactive Oxygen Species; D014280:Triglycerides; D002784:Cholesterol; D053148:Caspase 3; D005978:Glutathione; D001663:Bilirubin