Mechanisms of alcohol-induced hepatic fibrosis: A summary of the Ron Thurman Symposium

Purohit, Vishnudutt; Brenner, David A.

doi:10.1002/hep.21107

Cited by 149 publications

(133 citation statements)

References 60 publications

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“…One complication in this central role for TNFα is that hepatocytes are normally resistant to TNFα induced toxicity. This led to the hypothesis that besides elevating TNFα, alcohol somehow sensitizes or primes the liver to become susceptible to TNFα (201,202). Known factors which sensitize the liver to TNFα are inhibitors of mRNA or protein synthesis, which likely prevent the synthesis of protective factors, inhibition of NF-κB activation to lower synthesis of such protective factors, depletion of GSH, especially mitochondrial GSH, lowering of s-adenosyl methionine (SAM) coupled to elevation of S-adenosyl homocysteine (SAH) i.e.…”

Section: Lps/tnfα-cyp2e1 Interactionsmentioning

confidence: 99%

CYP2E1 and oxidative liver injury by alcohol

Cederbaum

2008

Free Radical Biology and Medicine

651

534

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Ethanol-induced oxidative stress appears to play a major role in mechanisms by which ethanol causes liver injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway appears to be the induction of cytochrome P450 2E1 (CYP2E1) by ethanol. CYP2E1 metabolizes and activates many toxicological substrates, including ethanol, to more reactive, toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions, and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide, and in the presence of iron catalysts, produces powerful oxidants such as the hydroxyl radical. This Review Article summarizes some of the biochemical and toxicological properties of CYP2E1, and briefly describes the use of cell lines developed to constitutively express CYP2E1 in assessing the actions of CYP2E1. Possible therapeutic implications for treatment of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help to understand the actions of CYP2E1 and its role in alcoholic liver injury.

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Section: Lps/tnfα-cyp2e1 Interactionsmentioning

confidence: 99%

CYP2E1 and oxidative liver injury by alcohol

Cederbaum

2008

Free Radical Biology and Medicine

651

534

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“…The replacement of normal liver with scar tissue also causes an irreversible decrease in liver function through the loss of normal liver tissue. 4 Fibrosis creates permanent scar tissue. 5 For this reason, liver cirrhosis is a disease that is difficult to treat and has a substantial morbidity and mortality rate.…”

Section: Introductionmentioning

confidence: 99%

Fluorescently Labeled Nanoparticles Enable the Detection of Stem Cell-Derived Hepatocytes

Ha¹,

Shin²,

Lee³

et al. 2012

Bulletin of the Korean Chemical Society

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Stem cell transplantation is emerging as a possible new treatment for liver cirrhosis, and recent animal studies have documented the benefits of stem cell therapy in a hepatic fibrosis model. However, the underlying mechanism of stem cell therapy is still unclear. Among the proposed mechanisms, the cell replacement mechanism is the oldest and most important, in which permanently damaged tissue can be replaced by normal tissue to restore function. In the present study, Cy5.5-labeled superparamagnetic iron oxide (SPIO) was used to label human mesenchymal stem cells. The uptake of fluorescently labeled nanoparticles enabled the detection and monitoring of the transplanted stem cells; therefore, we confirmed the direct incorporation and differentiation of SPIO into the hepatocyte-like transplanted stem cells by detecting human tyrosine aminotransferase (TAT), well-known enzymatic marker for hepatocyte-specific differentiation.

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“…11,12 In addition to simply enhancing liver injury, alcohol may accelerate progression of liver fibrosis through several mechanisms. [13][14][15] For instance, alcohol consumption may enhance hepatic HSC activation through an increase in gut-derived endotoxins, hypoxia (oxidative stress), or the formation of toxic and profibrogenic metabolites (eg, acetaldehyde or lipid peroxides). [13][14][15] Recently, we and others have shown that activation of the innate immune system, natural killer (NK) cells and interferon-γ (IFN-γ), inhibits liver fibrosis.…”

mentioning

confidence: 99%

“…[13][14][15] For instance, alcohol consumption may enhance hepatic HSC activation through an increase in gut-derived endotoxins, hypoxia (oxidative stress), or the formation of toxic and profibrogenic metabolites (eg, acetaldehyde or lipid peroxides). [13][14][15] Recently, we and others have shown that activation of the innate immune system, natural killer (NK) cells and interferon-γ (IFN-γ), inhibits liver fibrosis. [16][17][18] Moreover, the immunosuppressive effects of ethanol are well documented in alcoholics.…”

mentioning

confidence: 99%