Detection of circulating antibodies against malondialdehyde-acetaldehyde adducts in patients with alcohol-induced liver disease

Rolla, Roberta; Vay, Daria; Mottaran, Elisa; Parodi, M.; Traverso, Nicola; Aricò, S; Sartori, Massimo; Bellomo, Giorgio; Klassen, Lynell Warren; Thiele, Geoffrey M.; Tuma, Dean J.; Albano, Emanuele

doi:10.1053/he.2000.5373

Cited by 160 publications

(115 citation statements)

References 39 publications

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“…Low levels of ROS and high contents of GSH inhibit lipid peroxidation and liver necrosis. Conversely, high levels of ROS and low levels of GSH can be deleterious by enhancing lipid peroxidation and apoptosis (Peterhans 1997;Jones et al 1998;Vos et al 1999;Rolla et al 2000;Kaplowitz 2000). By inducing GSH depletion, ROS induce oxidative stress and reduce the antioxidant capability of other antioxidants (Huang et al 1998;Nishikawa et al 1998;Hall 1999).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Hyperbaric Oxygen Treatment on Oxidant and Antioxidants Levels during Liver Regeneration in Rats

Özden

Uzun

Bohloli

et al. 2004

Tohoku J. Exp. Med.

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The effects of hyperbaric oxygen (HBO) therapy on oxidant/antioxidant metabolism are controversial and its effects on hepatic regeneration are not known. In this study, we investigated a possible beneficial effect of HBO therapy on oxidant and antioxidants levels during liver regeneration. To conduct this study, seventy percent hepatectomy was performed on forty-eight SpraggueDawley rats and the rats were divided into two equal groups: HBO-treated group and untreated group (non-HBO group). We determined the levels of malondialdehyde (MDA), an oxidative stress marker, and the levels of antioxidant enzymes/reagents, including glutathione (GSH), superoxide dismutase (SOD) activitiy, copper (Cu) and zinc (Zn), in the remnant liver samples. We also measured mitotic index (MI) and proliferating cell nuclear antigen (PCNA) levels to assess the degree of liver regeneration. HBO treatment significantly decreased MDA levels, whereas it increased SOD activity, GSH and Zn levels. In contrast, Cu levels were lower in the HBO-treated livers than the levels in the untreated remnant livers. The effect of HBO treatment may be mediated by the suppression of certain enzymes that are responsible for lipid peroxidation. In addition, HBO treatment may induce the production of antioxidant enzymes/reagents by remnant liver tissues. The HBO-treated rats maintained their body weights but the untreated rats lost body weights. HBO treatment also increased MI and PCNA levels, indicating HBO treatment enhances liver regeneration. These

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Section: Discussionmentioning

confidence: 99%

The Effects of Hyperbaric Oxygen Treatment on Oxidant and Antioxidants Levels during Liver Regeneration in Rats

Özden

Uzun

Bohloli

et al. 2004

Tohoku J. Exp. Med.

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“…This effect is closely associated with the promotion of MDA and 4-hydroxynonenal formation as well as with an increase in transforming growth factor b1 and procollagen-a -1 mRNA expression in both the whole liver and freshlyisolated HSC . In human subjects elevated titres of antibodies towards lipid peroxidation adducts or oxidized phospholipids are prevalent in heavy drinkers with fibrosis or cirrhosis, irrespective of the magnitude and the duration of alcohol intake (Rolla et al 2000;Mottaran et al 2002). These antibodies are also higher in patients with severe cirrhosis (Child's (Child & Turcotte, 1964) grade B and C) as compared with those with the milder disease (Child's grade A), suggesting the possibility that an immune response involving lipid peroxidation antigens might also have a role in the progression of alcohol-induced liver damage to fibrosis.…”

Section: Free Radical Mechanisms In Immune Reactions Associated With mentioning

confidence: 99%

Alcohol, oxidative stress and free radical damage

2006

Self Cite

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The involvement of free radical mechanisms in the pathogenesis of alcoholic liver disease (ALD) is demonstrated by the detection of lipid peroxidation markers in the liver and the serum of patients with alcoholism, as well as by experiments in alcohol-feed rodents that show a relationship between alcohol-induced oxidative stress and the development of liver pathology. Ethanol-induced oxidative stress is the result of the combined impairment of antioxidant defences and the production of reactive oxygen species by the mitochondrial electron transport chain, the alcohol-inducible cytochrome P450 (CYP) 2E1 and activated phagocytes. Furthermore, hydroxyethyl free radicals (HER) are also generated during ethanol metabolism by CYP2E1. The mechanisms by which oxidative stress contributes to alcohol toxicity are still not completely understood. The available evidence indicates that, by favouring mitochondrial permeability transition, oxidative stress promotes hepatocyte necrosis and/or apoptosis and is implicated in the alcohol-induced sensitization of hepatocytes to the pro-apoptotic action of TNF-a. Moreover, oxidative mechanisms can contribute to liver fibrosis, by triggering the release of pro-fibrotic cytokines and collagen gene expression in hepatic stellate cells. Finally, the reactions of HER and lipid peroxidation products with hepatic proteins stimulate both humoral and cellular immune reactions and favour the breaking of self-tolerance during ALD. Thus, immune responses might represent the mechanism by which alcohol-induced oxidative stress contributes to the perpetuation of chronic hepatic inflammation. Together these observations provide a rationale for the possible clinical application of antioxidants in the therapy for ALD.

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“…For example, MDA/acetaldehyde hybrid adducts (MAAs) potentiate carcinogenic effect of single adducts [10,44,45] , thereby perpetuating their genotoxic effects. Autoantibodies against MMA were significantly elevated in sera of chronic alcoholexposed animals [46] and in patients with ALD, and the titers are correlated with the severity of liver damage [11,47,48] and progression of liver fibrosis. Interestingly, adducts accumulate in perivenous regions both in alcohol-fed rats [49,50] and in the liver of alcoholics [51,52] , overlapping with the distribution of fatty accumulation.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

Ceni

Mello

Galli

2014

WJG

388

339

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Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility. Key words: Alcohol metabolism; Acetaldehyde; Reactive oxygen species; Alcoholic liver disease; Protein adducts; Hepatic stellate cells; Liver fibrosis; CYP2E1Core tip: The goal of this article is to review the mechanisms of alcohol-mediated toxicity in parenchymal and non-parenchymal cells of the liver. Specifically, we highlight the effect of oxidative ethanol metabolites such as acetaldehyde and reactive oxygen species in the development of fat accumulation, fibrosis and deranged immune response.Ceni E, Mello T, Galli A. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism.

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Detection of circulating antibodies against malondialdehyde-acetaldehyde adducts in patients with alcohol-induced liver disease

Cited by 160 publications

References 39 publications

The Effects of Hyperbaric Oxygen Treatment on Oxidant and Antioxidants Levels during Liver Regeneration in Rats

The Effects of Hyperbaric Oxygen Treatment on Oxidant and Antioxidants Levels during Liver Regeneration in Rats

Alcohol, oxidative stress and free radical damage

Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

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