Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol

Kurose, Iwao; Higuchi, Hajime; Kato, Shinichi; Miura, Soichiro; Watanabe, Naoyuki; Kamegaya, Yoshitaka; Tomita, Kengo; Takaishi, M; Horie, Yoshinori; Fukuda, Masahiko; Mizukami, Ken; Ishii, Hiromasa

doi:10.1016/s0016-5085(97)70147-1

Cited by 115 publications

(66 citation statements)

References 3 publications

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“…Studies with isolated hepatocytes from control rats or chronic ethanol-fed rats indicated that ethanol metabolism via alcohol dehydrogenase results in an increase in ROS production, hepatocyte injury, and apoptosis, reactions blocked by antioxidants [1,9,47]. Studies in our laboratory with HepG2 cell lines expressing CYP2E1 showed that addition of ethanol or polyunsaturated fatty acids or iron, or depletion of GSH, resulted in cell toxicity, increased oxidative stress, and mitochondrial damage, reactions prevented by antioxidants [94,95].…”

mentioning

confidence: 99%

CYP2E1 potentiation of LPS and TNFα-induced hepatotoxicity by mechanisms involving enhanced oxidative and nitrosative stress, activation of MAP kinases, and mitochondrial dysfunction

Cederbaum

2009

Genes Nutr

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The mechanisms by which alcohol causes cell injury are not clear. A major mechanism that is the focus of considerable research is the role of lipid peroxidation and oxidative stress in alcohol toxicity. Many pathways have been suggested to play a role in how alcohol induces oxidative stress. Considerable attention has been given to alcohol-elevated production of lipopolysaccharide (LPS) and TNFa and to alcohol induction of CYP2E1. These two pathways are not exclusive of each other, however, associations and interactions between them, especially in vivo, have not been extensively evaluated. We have shown that increased oxidative stress from induction of CYP2E1 in vivo sensitizes hepatocytes to LPS and TNF toxicity and that oxidants, such as peroxynitrite, activation of p38 and JNK MAP kinases, inactivation of NF-kB protective pathways and mitochondrial dysfunction are downstream mediators of this CYP2E1-LPS/TNF potentiated hepatotoxicity. This review will summarize studies showing potentiated interactions between these two risk factors in promoting liver injury and the mechanisms involved.Keywords Alcohol Á CYP2E1 Á Lipopolysaccharide Á Oxidative stress Á Tumor necrosis factor alpha Alcohol, oxidative stress and cell injuryThe ability of acute and chronic ethanol treatment to increase production of reactive oxygen species and to enhance peroxidation of lipids, protein, and DNA has been demonstrated in a variety of systems, cells, and species, including humans [3]. Despite a tremendous growth in understanding alcohol metabolism and actions, the mechanism(s) by which alcohol causes cell injury are still not clear. A variety of leading mechanisms has been briefly summarized [13,17,67], and it is likely that many of them ultimately converge as they reflect a spectrum of the organism's response to the myriad of direct and indirect actions of alcohol. A major mechanism that is a focus of considerable research is the role of lipid peroxidation and oxidative stress in alcohol toxicity. Many pathways have been suggested to play a key role in how ethanol induces ''oxidative stress''. Some of these include redox state changes (decrease in the NAD ? /NADH redox ratio) produced as a result of ethanol oxidation by alcohol and aldehyde dehydrogenases; production of the reactive product acetaldehyde as a consequence of ethanol oxidation by all major oxidative pathways; damage to mitochondria which results in decreased ATP production; direct or membrane effects caused by hydrophobic ethanol interaction with either phospholipids or protein components or enzymes; ethanol-induced hypoxia, especially in the pericentral zone of the liver acinus as oxygen is consumed in order for the liver to detoxify ethanol via oxidation; ethanol effects on the immune system, and altered cytokine production; ethanol-induced increase in bacterialderived endotoxin with subsequent activation of Kupffer cells; ethanol induction of CYP2E1; ethanol mobilization of iron which results in enhanced levels of low molecular weight non-heme iron; effects...

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confidence: 99%

CYP2E1 potentiation of LPS and TNFα-induced hepatotoxicity by mechanisms involving enhanced oxidative and nitrosative stress, activation of MAP kinases, and mitochondrial dysfunction

Cederbaum

2009

Genes Nutr

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“…ROS may cause mitochondrial dysfunction and affect the release of pro-apoptotic factors, such as cytochrome c, with the consequence of caspase activation (11,50). In line with this, antioxidants have been shown to reduce apoptosis in ethanol-exposed rats (56,57). ROS may increase FasL mRNA expression in hepatocytes and activate autocrine or paracrine mechanisms of cell death.…”

Section: Apoptosis In Ethanol-induced Liver Diseasementioning

confidence: 88%

Apoptosis in selected liver diseases

Kiliçarslan

Kahraman²,

Akkız³

et al. 2009

Turk J Gastroenterol

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“…13 Ethanol is metabolized in liver through oxidation, causes accumulation of reactive oxygen species (ROS); like superoxide, hydroxyl radical, and hydrogen peroxide, 14 ultimately leading to injury of hepatocytes. [15][16][17] These are considered associated with ethanolic liver disease (ALD). Chronic ethanol intake leads to many cellular and tissue abnormalities; thereby leakage of cellular enzymes and other related biochemical parameters.…”

Section: Discussionmentioning

confidence: 99%

Identification of Bioactive Compounds and Possible Mechanism of Hepatoprotective Activity of Ficus microcarpa l. Fil. Bark Extracts in Ethanol-Induced Chronic Hepatic Injury in Rats

Surana¹,

Tatiya²,

Kalaskar³

2017

IJPER

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Objective: To evaluate the effect of the successive extracts of the FMB on ethanol induced chronic hepatotoxicity. Furthermore, to understand the mechanisms of its pharmacological actions, the in vivo antioxidant activity and major phytoconstituents of FMB were investigated. Methodology: Ficus microcarpa L. fil., (FM) is commonly known as 'Indian Laurel', is used for liver complaints in Indian traditional practice. The hepatoprotective effect of four successive extracts (petroleum ether 60-80o, ethyl acetate, ethanol and aqueous) of FM bark (FMB) were studied in chronic ethanol induced liver damage. The protective potential measured by monitoring biochemical parameters and histopathological alterations. Result: The ethyl acetate extract of FMBE produce significant hepatoprotection by stabilizing the biochemical parameters in a dose dependent manner, comparable to that of standard drug, silymarin; also showed the positive involvement of endogenous antioxidant system. Further, it was confirmed by histology examination of liver. Phytochemical studies confirmed the presence of the phenolic and triterpenoids compounds such as catechin, oleanolic and betulinic acid. Conclusion: Hepatoprotective ability of FMB involves antioxidant mechanism associated with up-regulation of endogenous antioxidant system due to presence of phenolics and triterpenoids. Thus, the present study provides a scientific rationale for the traditional use in the management of chronic liver disorders.

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Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol

Cited by 115 publications

References 3 publications

CYP2E1 potentiation of LPS and TNFα-induced hepatotoxicity by mechanisms involving enhanced oxidative and nitrosative stress, activation of MAP kinases, and mitochondrial dysfunction

CYP2E1 potentiation of LPS and TNFα-induced hepatotoxicity by mechanisms involving enhanced oxidative and nitrosative stress, activation of MAP kinases, and mitochondrial dysfunction

Apoptosis in selected liver diseases

Identification of Bioactive Compounds and Possible Mechanism of Hepatoprotective Activity of Ficus microcarpa l. Fil. Bark Extracts in Ethanol-Induced Chronic Hepatic Injury in Rats

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