Mechanisms of alcohol-induced hepatotoxicity studies in rats

Thurman, Ronald G.; Bradford, Blair U.; Iimuro, Yuji; Frankenberg, Moritz von; Knecht, Kathryn T.; Connor, Henry D.; Adachi, Yoshifumi; Wall, Chantal; Arteel, Gavin E.; Raleigh, James A.; Forman, Donald T.; Mason, Ronald P.

doi:10.2741/a478

Cited by 37 publications

(29 citation statements)

References 24 publications

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“…Many recent studies suggest that several proinflammatory cytokines produced by activated Kupffer cells might be involved in the onset of alcoholic liver disease (4,5). For instance, elevated circulating levels of TNF-α, IL-1β, and IL-6 have been observed in human patients and animal models of alcohol-induced liver injury (6,7). The expression levels of these cytokines correlate well with the course of the disease.…”

Section: Introductionmentioning

confidence: 82%

The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice

et al. 2003

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Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of highfat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-α and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.

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Section: Introductionmentioning

confidence: 82%

The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice

et al. 2003

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“…The importance of TNFα and its receptor I in the onset of hepatotoxicity and cellular apoptosis has been indicated in both patients (McClain et al, 1999) and animal models (Thurman et al, 1999;Tilg and Diehl, 2000) with NASH and alcohol-related liver injury. However, the little difference of TNFα and TNFR1 expressions between the HFA and HFD groups seems to exclude their potential contribution to moderate alcohol-induced further increase of cellular apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats

Wang¹,

Seitz²,

Xd³

2010

Z Gastroenterol

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“…1,2 The effects of ethanol on hepatocyte function are diverse and range from an increased pro-oxidative state and acetaldehyde adduct formation to interference with cellular signaling processes associated with stress defenses. One of the primary sites manifesting damage brought on by ethanol is the mitochondria.…”

mentioning

confidence: 99%

Ethanol potentiates tumor necrosis factor-α cytotoxicity in hepatoma cells and primary rat hepatocytes by promoting induction of the mitochondrial permeability transition

2000

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Mechanisms of alcohol-induced hepatotoxicity studies in rats

Cited by 37 publications

References 24 publications

The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice

The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice

Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats

Ethanol potentiates tumor necrosis factor-α cytotoxicity in hepatoma cells and primary rat hepatocytes by promoting induction of the mitochondrial permeability transition

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