Liver injury ethanol-induced

Alcohol abuse is a major clinical problem in many countries and has been the subject of investigation for many years by those interested in determining the molecular basis of ethanol-induced liver dam e (see Lieber, 1990). These intensive and extended efforts have revealed much about the metabolism of ethanol in the liver and about the toxicity of its primary oxidative product, acetaldehyde. They have not, however, folly elucidated the molecular mechanisms that lead to the typical features of alcoholic liver injury steatosis, necrosis and eventually cirrhosis. 

A relatively recent study of significance to the putative involvement of lipid peroxidation in ethanol-induced 

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D. (1991). The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury. Drug Alcohol Depend. 28, 291-294. 

Shaw, D.S. and Jayatilleke, E. (1992). The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury. Life Sci. 50, 2045-2052. 

Beneficial effects of camosine have been described with respect to ethanol-induced liver injury in mice (Liu et al., 2008a,b). It was found that following 3 weeks of ethanol treatment (present in drinking water), subsequent exposure to camosine decreased liver malondialdehyde... 

Kessova, I., and A.I. Cederbaum. 2003. CYP2E1 Biochemistry, toxicology, regulation and function in ethanol-induced liver injury. Curr. Mol. Med. 3(6) 509-518. 

Increased serum and/or tissue TNF levels have been observed in alcoholic liver disease (see Chapter 47), and TNF has been postulated to play a role in ethanol-induced liver injury. It appears that both TNF and ethanol are capable of increasing manganese superoxide dismutase activity, presumably via enhanced oxidative stress. ... 

Influence of Nutritional Status and Tryptophan on Ethanol-Induced Liver Injury... 

Saravanan, N., and N. Nalini. 2007c. Inhibitory effect of Hemidesmus indicus and its active principle 2-hydroxy-4-methoxybenzoic acid on ethanol-induced liver injury. Fun m. Clin. Pharmacol. 21(5) 507-514. 

Towner RA, Reinke LA, Janzen EG, et al. 1991. Enhancement of carbon tetrachloride-induced liver injury by a single dose of ethanol proton magnetic resonance imaging (MRI) studies In vivo. Acta Biochem Biophys 1096 222- 230. 

Liu, W. H., Liu, T. C., and Yin, M. C. (2008a). Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. Food Chem. Toxicol. 46,1503-1509. 

Haloalkanes. Certain haloalkanes and haloalkane-containing mixtures have been demonstrated to potentiate carbon tetrachloride hepatotoxicity. Pretreatment of rats with trichloroethylene (TCE) enhanced carbon tetrachloride-induced hepatotoxicity, and a mixture of nontoxic doses of TCE and carbon tetrachloride elicited moderate to severe liver injury (Pessayre et al. 1982). The researchers believed that the interaction was mediated by TCE itself rather than its metabolites. TCE can also potentiate hepatic damage produced by low (10 ppm) concentrations of carbon tetrachloride in ethanol pretreated rats (Ikatsu and Nakajima 1992). Acetone was a more potent potentiator of carbon tetrachloride hepatotoxicity than was TCE, and acetone pretreatment also enhanced the hepatotoxic response of rats to a TCE-carbon tetrachloride mixture (Charbonneau et al. 1986). The potentiating action of acetone may involve not only increased metabolic activation of TCE and/or carbon tetrachloride, but also possible alteration of the integrity of organelle membranes. Carbon tetrachloride-induced liver necrosis and lipid peroxidation in the rat has been reported to be potentiated by 1,2- dichloroethane in an interaction that does not involve depletion of reduced liver glutathione, and that is prevented by vitamin E (Aragno et al. 1992). 

Seo YS, Kwon JH, Yaqoob U, Yang L, de Assuncao TM, Simonetto DA, Verma VK, Shah VH (2013) HMGB1 recruits hepatic stellate cells and liver endothelial cells to sites of ethanol induced parenchymal cell injury. Am J Physiol Gastrointest Liver Physiol. doi 10.1152/ajpgi.00151.2013... 

The endoplasmic reticulum (ER) contributes to a variety of functions, including protein synthesis and detoxification of xenobiot-ics, and disturbance of these functions can be linked to cell injury (53). Prolonged exposure to ethanol induces proliferation of the ER of in the liver and enhanced activity of cytochrome P450 enzymes, which in turn can result in production of hepatotoxic or carcinogenic metabolites (54). 

LocaUzation of a specific adduct in tissue provides a visual fixed point of reference from which further questions may be posed regarding other correlates of injury altered structure or function and quantification of adduct. In the case of acetaminophen adducts in the liver, we showed that moi-phologic evidence of cell injury (histology), coincided consistently in time and location with quantity of localized adduct. Functional measurements revealed that clinical evidence of hepatic dysfunction also were proportional to histologic evidence of localized adduct and of injury. The concordance between adduct visualized in tissue sections and adduct measured in Uver homogenates by quantitative immunoassay was temporally consistent as the adduct accumulated and also later as the adduct leaked fi-om damaged cells and appeared in serum (7). Other correlations that strengthened the postulated mechanism of acetaminophen hepatotoxicity were the depletion of hepatic GSH antecedent to cell injury, and the coincident distribution of localized adduct, tissue injury, and ethanol-inducible P-450. 

Li J, Jiang Q-G, Zhcxig W-D. Persistent ethanol drinking increases liver injury induced by trinitrotoluene exposure an in-plant case-control studjy. HumExp Taxicol(l99l) 10,405-9. 

Several animal studies have indicated that extracts of platycodon or saponins from platycodon prevented liver injury and changes in liver enzyme levels induced by ethanol or carbon tetrachloride. These studies indicated that inhibition of the drug-metabolizing isoenzyme CYP2E1 was responsible for this protection. Doses used in these studies were 10 to 100 mg/kg of an aqueous extract or 0.5 to 2 mg/kg of saponins (Khanal et al. 2009 Kim et al. 2007 Lee et al. 2008 Lee and Jeong 2002). 

Khan AQ, Nafees S, Sultana S (2011) Perillyl alcohol protects against ethanol induced acute liver injury in Wistar rats by inhibiting oxidative stress, NFk-B activation and proinflammatory cytokine production. Toxicology 279(1-3) 108-114... 

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