Acute Alcohol-Induced Liver Injury

Abstract

Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD) in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation, and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, which also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

Current evidence on the use of probiotics in liver diseases

“…While alcohol may be sufficient to cause fat accumulation, it is not the only mechanism by which steatosis develops such as blocking or altering cell signaling, genetic alterations, pro-inflammatory mediators (Massey & Arteel, 2012). Furthermore, chronic ingestion of ethanol increases acetaldehyde, a major toxic metabolic intermediate of alcohol detoxification that causes direct DNA damage, leads to the production of several end-products which contribute to the pathogenesis of ALD (Hayashi et al, 2013).…”

Alcohol Modulation of the Postburn Hepatic Response

“…The resulting hepatic fatty infiltration is associated with increased incidence of sepsis and mortality in pediatric burn patients [67], highlighting the importance of organ integrity. Steatosis is also commonly caused by alcohol consumption [114] and the degree of steatosis is substantially increased in mice with the combination of alcohol and burn over either insult alone [20,22]. Animal studies show that alcohol metabolism increases the ratio of NADH:NAD+ which then inhibits β-oxidation of fatty acids while increasing the rate of their esterification [115], leading to excessive triglyceride storage.…”

Sinusoidal endothelial cell-derived extracellular matrix regulates basal and stimulated macrophage activation.

“…After three washes, the extracellular matrix deposited by the TSECs was used as a substratum for culturing RAW 264.7 cells (11,12). RAW 264.7 cells (passage [4][5][6][7][8][9][10][11][12][13][14] were seeded at a density of 150,000 cells per well in 1.0 mL of media on the preserved TSEC ECM or in control wells and incubated for 24 hours. Then, cells were exposed to LPS (100 ng/mL) ± CycloRGDfV (10 µM) for an additional 3, 6, 12, or 24 hour incubation period.…”

“…Integrin  v  3 binds fibrin ECM through interaction with the RGD (arginine-glycene-aspartate) sequence on the ECM (7). When this interaction is blocked using the small peptide antagonist CycloRGDfV, LPS-induced liver injury caused by acute alcohol exposure is blunted with no effect on fibrin accumulation (6). These data suggest that liver injury and inflammation may be due, at least in part, to interaction between fibrin ECM and the integrin  v  3 .…”

“…One mechanism by which ECM components may contribute to inflammation is through interaction with cell surface adhesion receptors known as integrins (6). For example, fibrin ECM interacts with the integrin  v  3 , a receptor known to contribute to inflammation, tumor angiogenesis, and metastasis (7,8).…”