Chapter 3

Antioxidants as a Therapeutic Option in Inflammatory Liver Diseases with a Metabolic Origin

María de Fátima Higuera-de la Tijera and Alfredo Israel Servín-Caamaño

Abstract

The inflammatory liver diseases with a metabolic origin, such as alcoholic liver disease (ALD) and nowadays, non-alcoholic fatty liver disease (NAFLD) associated to the growing epidemic of metabolic syndrome, are two important health care problems and common causes of cirrhosis and its complications in developed countries and worldwide. The physiopathology of these conditions, importantly involves oxidative stress. In ALD, alcohol metabolism comes from oxidative and nonoxidative pathways. The oxidative pathway involves two major enzymes, alcohol dehydrogenase (ADH), which oxidizes alcohol to acetaldehyde, and acetaldehyde dehydrogenase (ALDH) that transforms acetaldehyde to acetate. Acetaldehyde is a cardinal toxin involved in alcohol-related liver injury. Reduced nicotinamide dinucleotide (NADH) generated by these enzymatic reactions also contributes to harm. The oxidation of alcohol also occurs via cytochrome P450 to cause liver damage by producing reactive oxygen species (ROS) that are guilty of activating redox-sensitive transcription factors, such as nuclear factor-kappaB (NF-kB), triggering and perpetuating a pro-inflammatory status. Similarly, oxidative stress, in addition to insulin resistance, is considered as a main factor contributing to liver injury in patients with non alcoholic steatohepatitis (NASH). Recently, oxidative stress constitutes a novel and attractive target for therapy, in ALD, NAFLD and NASH.

Total Pages: 80-105 (26)

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