Oxidative stress and inflammation: essential partners in alcoholic liver disease

Abstract

Alcoholic liver disease (ALD) is a multifaceted disease that is characterized by hepatic steatosis or fat deposition and hepatitis or inflammation. Over the past decade, multiple lines of evidence have emerged on the mechanisms associated with ALD. The key mechanisms identified so far are sensitization to gut-derived endotoxin/lipopolysaccharide resulting in proinflammatory cytokine production and cellular stress due to oxidative processes, contributing to the development and progression of disease. While oxidative stress and inflammatory responses are studied independently in ALD, mechanisms linking these two processes play a major role in pathogenesis of disease. Here we review major players of oxidative stress and inflammation and highlight signaling intermediates regulated by oxidative stress that provokes proinflammatory responses in alcoholic liver disease.

Figure 1

Oxidative stress and inflammation: interacting mechanisms in ALD. The development of alcoholic liver injury is a complex process involving oxidative stress microenvironment in the liver contributed by hepatocytes and macrophages. In addition to the activation of macrophages by gut-derived endotoxin, cellular stress responses contribute to proinflammatory cytokine production creating a tightly interrelated network in ALD.