1. Oxidants and antioxidants in alcohol-induced liver disease
Gavin E. Arteel 
Gastroenterology 
Volume 124, Issue 3, Pages (March 2003)
DOI: /gast
Copyright © 2003 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Potential pathways of formation of potent oxidants from superoxide. Superoxide (O2·−) can react through catalytic pathways in the cell to form more potent oxidants. For example, the reduction of O2·− by SOD forms H2O2; H2O2 and transition metals can lead to formation of hydroxyl radicals (the Fenton reaction).21 Alternatively, H2O2 can react with Cl− via myeloperoxidase in neutrophils to make HOCl−.22 An additional pathway of O2·−-dependent oxidative stress involves the enzyme independent reaction of O2·− with NO· to form ONOO−, a strong oxidizing and nitrating species.23,24
Gastroenterology  , DOI: ( /gast )
Copyright © 2003 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Working hypothesis on the cell-cell interactions in oxidant-mediated cell-death during alcohol-induced liver injury. Oxidant production from Kupffer cells in liver leads to activation of oxidant-sensitive signaling pathways, which prime the cells to LPS activation. Further, activation of oxidant-sensitive transcription factors (e.g., NFκB), increases the formation of proinflammatory/cytotoxic cytokines, such as TNFα. In hepatocytes, the stimulus of oxidant production caused by alcohol leads to a sensitization of the cells to cytotoxic signaling (e.g., from TNFα) through apoptotic/necrotic signaling pathways. Therefore, oxidative stress is likely to occur in at least 2 compartments in the liver and oxidative stress-induced liver injury involves coordination of signaling events within and between these compartments.
Gastroenterology  , DOI: ( /gast )
Copyright © 2003 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Possible mechanisms by which TNFα and other cytokines contribute to steatosis during alcohol-induced liver injury. Direct effects of TNFα include increased free fatty acid (FFA) release from adipocytes in the periphery,110 increased lipogenesis in hepatocytes,111 and inhibition of β-oxidation of fatty acids.112 Taken together, the net amount of FFA in hepatocytes is increased. Further, TNFα can directly increase ROS formation by impairing mitochondrial electron flow, leading to formation of O2·−. Indirectly, the oxidation of lipids by ROS/RNS can further impair β-oxidation of fatty acids, and further damage mitochondria. Other cytokines induced by alcohol (e.g., IL-1 and IL-6), may impair transport and secretion of triglycerides (TG).113 The net result during alcohol exposure is that cytokines increase the supply of fatty acids to liver, while simultaneously impairing the ability of the hepatocytes to metabolize and secrete them. It is proposed that these effects work in tandem with alcohol-induced shifts in the NADH redox state to lead to steatosis.
Gastroenterology  , DOI: ( /gast )
Copyright © 2003 American Gastroenterological Association Terms and Conditions