Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

Mantena, Sudheer K.; King, Adrienne L.; Andringa, Kelly K.; Landar, Aimee; Darley‐Usmar, Victor; Bailey, Shannon M.

doi:10.3748/wjg.v13.i37.4967

Cited by 54 publications

(45 citation statements)

References 78 publications

(88 reference statements)

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“…From the pathophysiologic perspective, the increase in IMAR levels with disease severity provides evidence of protein modification, which in keeping with the published literature has been shown to be associated with severity of oxidative stress. 21,22 The use of EPR spectra provides data regarding changes in fatty acid binding of serum albumin under modulation of medium hydrophilicity and allows conclusions for transport and detoxification capacity of this integral plasma protein. 16,17,21 The efficiency of the albumin transport system depends on two factors.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality

Schnurr²,

et al. 2009

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Albumin concentration is diminished in patients with liver failure. Albumin infusion improves survival of cirrhotic patients with spontaneous bacterial peritonitis, and it is hypothesized that this may be due in part to its detoxifying capabilities. The aim of this study was to perform detailed quantitative and qualitative assessment of albumin function in patients with cirrhosis. Healthy controls and patients with acute deterioration of cirrhosis requiring hospital admission (n ‫؍‬ 34) were included. Albumin function was assessed using affinity of the fatty acid binding sites using a spin label (16 doxyl-stearate) titration and electron paramagnetic resonance spectroscopy and ischemia-modified albumin (IMA) was measured. Twenty-two patients developed acute-on-chronic liver failure. Twelve were treated with the Molecular Adsorbents Recirculating System (MARS) and 10 with standard medical therapy. For each parameter measured, the patients' albumin had reduced functional ability, which worsened with disease severity. Fifteen patients died, and IMA, expressed as an albumin ratio (IMAR), was significantly higher in nonsurvivors compared with survivors (P < 0.001; area under the receiver operating curve ‫؍‬ A lbumin is the major plasma protein and constitutes around 50% of the cell free protein in healthy individuals. It is produced exclusively in the liver, and therefore its concentration is reduced during hepatic dysfunction. 1 Following the Cochrane meta-analysis describing potential harmfully effect of albumin infusion in critically ill patients, there has been a reexamination of the use of albumin infusions for volume replacement. However, the results of the recently published SAFE study have provided new data confirming the safety of albumin infusion in critically ill patients. 2,3 Liver failure results in multiple organ dysfunction, and mortality rates without liver transplantation remain unacceptably high. 4 However, recovery is associated with complete reversal of multiorgan dysfunction. At present, in patients with cirrhosis, albumin is used mainly to replenish the circulating volume. With increasing severity of cirrhosis, there is a progressive increase in cardiac output, which is associated with a progressive reduction in individual organ blood flow. This peculiar circulatory disturbance is thought to occur as a result of splanchnic

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Section: Discussionmentioning

confidence: 99%

Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality

Schnurr²,

et al. 2009

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“…Possible mechanisms for enhanced mitochondrial ROS production include molecular defects within Complexes I and III, as well as increases in RLS, and TNFα mediated ceramide [22,59,62,63]. See review [64] for a detailed description of the mechanisms responsible for alcohol induced increases in mitochondrial ROS.…”

Section: Mitochondria Dysfunction In Fatty Liver Diseases -Bioenergetmentioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Mantena

King

Andringa

et al. 2008

Free Radical Biology and Medicine

382

302

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Fatty liver disease associated with chronic alcohol consumption or obesity/type 2 diabetes has emerged as a serious public health problem. Steatosis, accumulation of triglyceride in hepatocytes, is now recognized as a critical "first-hit" in the pathogenesis of liver disease. It is proposed that steatosis "primes" the liver to progress to more severe liver pathologies when individuals are exposed to subsequent metabolic and/or environmental stressors or "second-hits". Genetic risk factors can also influence the susceptibility and severity of fatty liver disease. Furthermore, oxidative stress, disrupted nitric oxide (NO) signaling, and mitochondrial dysfunctional are proposed to be key molecular events that accelerate or worsen steatosis and initiate progression to steatohepatitis and fibrosis. This review article will discuss the following topics regarding the pathobiology and molecular mechanisms responsible for fatty liver disease: 1) the "two-hit" or "multi-hit" hypothesis; 2) the role of mitochondrial bioenergetic defects and oxidant stress; 3) interplay between NO and mitochondria in fatty liver disease; 4) genetic risk factors and oxidative stress responsive genes; and 5) the feasibility of antioxidants for treatment.

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“…Moderate consumption may induce some positive effects, 1,2) but massive consumption sometimes causes hepatic diseases such as fatty liver, alcoholic hepatitis, liver cirrhosis, and liver cancer. [3][4][5][6] In these cases, inflammatory events are involved in the development of alcoholic liver injury. Hepatic inflammation may be prevented by several endogenous factors including the antioxidant enzyme catalase and superoxide dismutases (SODs); 7,8) these enzymes possibly play a role in the prevention of alcoholic liver damage as well.…”

Section: Introductionmentioning

confidence: 99%

Hepatic Cytochrome P450 2E1 Level Rather Than Cecal Condition Contributes to Induction of Early Stage of the Alcoholic Liver Damage in Rats

Hashimoto

Sekiguchi

Masunaka

et al. 2009

JOURNAL OF HEALTH SCIENCE

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Intestinal condition and ethanol toxicity have been discussed as predictors of alcoholic liver damage. In this study, we investigated the association of hepatic antioxidant enzymes and cecal condition, including intestinal bacteria estimated by terminal restriction fragment length polymorphism (T-RFLP), in the early stage of alcoholic fatty liver. Three liquid isocaloric diets, control (CT) diet, ethanol (ET) diet, or ethanol diet including modified beet fiber (MBF), were prepared and administered to rats for 4 weeks. At 4 weeks, the plasma alanine aminotransferase (ALT) levels in the ET group were higher and that in MBF groups tended to be higher than the CT group, but endotoxin was not detected in the portal vein in any of the samples. The hepatic thiobarbituric acid reactive substances (TBARS) concentration in the MBF group was higher than that in the CT group. Hepatic cytochrome P450 2E1 (CYP2E1) was induced in ethanol-fed rats. The hepatic catalase levels in the ET and MBF groups were lower than that in the CT group. The hepatic superoxide dismutase-2 (SOD-2) level did not differ among the groups. Plasma ALT level and/or hepatic TBARS level correlated positively with CYP2E1 and negatively with catalase level and SOD-2 level. Indicators of cecal condition, including the bacterial population estimated by T-RFLP, may not give any explanation for the hepatic damage. In conclusion, the hepatic CYP2E1 induced by ethanol, rather than the cecal conditions, may influence the early stage of alcoholic hepatic damage in rats; hepatic catalase may provide protective effects.

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Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

Cited by 54 publications

References 78 publications

Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality

Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Hepatic Cytochrome P450 2E1 Level Rather Than Cecal Condition Contributes to Induction of Early Stage of the Alcoholic Liver Damage in Rats

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