Binge ethanol exposure increases liver injury in obese rats

Carmiel-Haggai, Michal; Cederbaum, Arthur I.; Nieto, Natalia

doi:10.1053/j.gastro.2003.09.019

Cited by 92 publications

(83 citation statements)

References 66 publications

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“…In normal healthy liver iNOS levels are very low or undetectable [91], whereas during inflammation and other disease states iNOS levels are increased in liver due to infiltrating inflammatory cells and via induction in Kupffer cells (resident liver macrophage), hepatocytes, and biliary epithelial cells [92][93][94]. Studies also report increased iNOS expression in liver of ob/ob mice [53], CCl 4 -induced steatotic liver following normothermic ischemia [95], and in the obese fa/fa rat exposed to binge alcohol [5]. This is important for hepatotoxicity because NO and peroxynitrite (ONOO − ) are known to mediate mitochondrial dysfunction [96,97] and increases in iNOS expression in fatty liver are correlated with nitration of mitochondrial proteins [53,98].…”

Section: Interplay Between Nitric Oxide and Mitochondria In Fatty LIVmentioning

confidence: 99%

“…Importantly, epidemiologic evidence demonstrates that alcohol, tobacco smoke, and obesity are synergistic risk factors for hepatocellular carcinoma [4]. Similarly, short-term binge alcohol exposure increases apoptosis and liver injury in obese rats compared to lean controls via increased oxidative stress [5]. Thus, there is clearly support for the concept that conditions of the cardiometabolic syndrome may exacerbate the hepatotoxic potential of alcohol in the liver and vice-versa.…”

Section: Introductionmentioning

confidence: 99%

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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

388

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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Section: Interplay Between Nitric Oxide and Mitochondria In Fatty LIVmentioning

confidence: 99%

Section: Introductionmentioning

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

388

302

View full text Add to dashboard Cite

show abstract

“…A detailed analysis of the composition of this diet can be found in table 1. Half of the rats were gavaged for three months with 1.5 ml/100 g body wt of whiskey (Johnnie Walker® Red Label) three times per wk as described (11,14), and the other half were gavaged with saline solution using a 12-gauge gavage needle. Whiskey was chosen, rather than pure alcohol, to simulate human drinking even knowing that a potential pitfall of our study was the presence of low percentage of impurities in commercial whiskey.…”

Section: Animal Study Designmentioning

confidence: 99%

“…Repeated alcohol binges disturb microcirculation in fatty grafts after liver transplantation, and oxidative stress is considered to play an important role, although the mechanism remains unclear (10). In mice, ethanol binge drinking induces hepatic oxidative stress, elevates levels of CYP2E1, and causes transient hepatic mitochondrial DNA depletion followed by increased mitochondrial DNA synthesis (11,12).…”

Section: Introductionmentioning

confidence: 99%

Repeated whiskey binges promote liver injury in rats fed a choline-deficient diet

Nieto

Rojkind

2007

Journal of Hepatology

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“…Obesity has been shown to be one of the conditions that decreases antioxidant capacity. [3][4][5][6] Obesity seems to decrease antioxidant defense by lowering the antioxidant enzymes, for example, catalase, glutathione peroxidase, glutathione reductase and by altering the activity of cytochrome P-450. Furthermore, previous studies have also reported that obese persons had lower concentrations of glutathione in erythrocytes.…”

Section: Introductionmentioning

confidence: 99%

Increased glutathione conjugate transport: a possible compensatory protection mechanism against oxidative stress in obesity?

et al. 2005

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Objective: To compare glutathione S-conjugate transport in obese and nonobese persons, and how glutathione S-conjugates are involved in the antioxidant status in obesity. Materials and methods: The efflux of glutathione conjugates and malondialdehyde (MDA) levels were measured in erythrocytes of obese (N ¼ 33) and nonobese (N ¼ 28) persons at every 30 min during a 120 min incubation time in vitro. 2,4-dinitrophenyl-S-glutathione (DNP-SG) represented the glutathione S-conjugate. Results: The efflux of conjugate in erythrocytes from obese subjects (7087147 DNP-SG efflux nmol/ml erythrocytes/h) was significantly higher than that of control group (4907105 DNP-SG efflux nmol/ml erythrocytes/h) (Po0.05). At all time points measured (30-120 min), there was an increase in DNP-SG efflux in obese group (Po0.05). This is manifested by a decrease in cellular DNP-SG levels. The susceptibility of erythrocytes to in vitro 1-chloro-2,4-dinitrobenzene (CDNB)-induced oxidative stress were greater for cells of control group (Po0.05), although hemolysis sensitivity of these cells are not different between both groups (P40.05). Following CDNB pretreatment, incubation of erythrocyte with vanadate, a DNP-SG transport inhibitor, resulted in an increase of MDA in both groups. However, in this case, the difference in susceptibility was not related to obesity. On the other hand, while erythrocyte glutathione level was lower in obese subjects (79% of control) than in controls (Po0.05), the adenosine 5 0 -triphosphate (ATP) levels, the enzyme activities of glutathione S-transferase (GST) and the conjugation capacities of the erythrocytes were not different between groups (P40.05). Conclusion: Obesity may increase erythrocyte glutathione conjugate transport independent from ATP and GST activity that may protect against MDA formation in vitro.

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Binge ethanol exposure increases liver injury in obese rats

Cited by 92 publications

References 66 publications

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

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

Repeated whiskey binges promote liver injury in rats fed a choline-deficient diet

Increased glutathione conjugate transport: a possible compensatory protection mechanism against oxidative stress in obesity?

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