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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 9895176, 13 pages
http://dx.doi.org/10.1155/2016/9895176
Research Article

Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

1Postgraduate Program in Experimental Biology, DCBS, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico
2Health Science Department, Universidad Autónoma Metropolitana Iztapalapa, 09340 Mexico City, DF, Mexico
3Translational Research Unit, Medica Sur Clinic and Foundation, 14050 Mexico City, DF, Mexico
4Department 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
5Laboratory 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
6Red “Fisiopatología de Enfermedades Hepáticas” PRODEP-SEP, 09340 Mexico City, DF, Mexico
7General Surgery Service 304, General Hospital of Mexico, UNAM School of Medicine, 06726 Mexico City, DF, Mexico
8Research Center for Alcohol Liver and Pancreatic Diseases and Cirrhosis, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Received 2 May 2016; Accepted 13 July 2016

Academic Editor: Ravirajsinh Jadeja

Copyright © 2016 Natalia Nuño-Lámbarri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.