Oxidative stress in chronic hepatitis C: not just a feature of late stage disease

Jain, Sanjiv; Pemberton, Philip W.; Smith, Alwyn; Mcmahon, Raymond; Burrows, P.C.; Aboutwerat, Ali; Warnes, Thomas W.

doi:10.1016/s0168-8278(02)00060-0

Cited by 177 publications

(168 citation statements)

References 46 publications

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“…26,34,35 In addition, we simultaneously evaluated oxysterols and ␣-tocopherol, obtaining a more detailed picture of the oxidant/ antioxidant balance in the same plasma sample of each patient. In agreement with previous studies on urinary and plasma isoprostanes 16,22 and on plasma ␣-tocopherol, 19,36 we found a deterioration of the constitutive antioxidant ␣-tocopherol that paralleled the increase in oxysterol concentration in plasma of patients with chronic hepatitis and in a more pronounced way in those with cirrhosis, as compared to healthy controls, suggesting evidence of increased radical flux in vivo as the natural history of chronic liver disease progresses. These findings are consistent with the kinetics of lipid peroxidation in vitro during which the evolution of oxidation products is preceded by consumption of constitutive antioxidants.…”

Section: Discussionsupporting

confidence: 92%

“…26,32 MDA assays, albeit useful in in vitro systems, are unsatisfactory and give contrasting results when applied in vivo. In fact, increased blood levels of MDA were found in HCV chronic liver disease C by Yadav et al 21 but not by Jain et al, 16 who, however, found increased levels of urinary isoprostanes, the gold standard for the assessment of systemic oxidative injury in vivo. 33 In the present study, we used a specific mass spectrometric assay of plasma 7␤-hydroxycholesterol and 7-ketocholesterol, validated markers of lipid peroxidation in vivo which have been previously demonstrated as being elevated in several clinical conditions characterized by high systemic oxidative stress status.…”

Section: Discussionmentioning

confidence: 97%

“…First, oxidative stress is involved in the pathogenesis of chronic liver disease and fibrosis, and increased oxidative stress with impaired antioxidant status at the systemic level has been described in different chronic liver diseases. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Second, two previous studies have shown the persistence of increased systemic lipid peroxidation products above normal values in patients with cirrhosis 3 to 12 weeks after OLT that is a likely expression of extrahepatic ROS production. In fact, this time frame from operation is too wide to be compatible with continuous intra-graft production of ROS secondary to ischemia-reperfusion injury and release into the circulation, and it is too small to be expression of chronic liver damage of the transplanted liver.…”

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confidence: 99%

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High preoperative recipient plasma 7β-hydroxycholesterol is associated with initial poor graft function after liver transplantation

et al. 2005

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Oxidative stress is implicated in the pathogenesis of hepatic ischemia-reperfusion injury, a major determinant of initial poor graft function (IPGF) after orthotopic liver transplantation (OLT). We prospectively investigated the association between the recipient plasma preoperative oxidative stress and the occurrence of IPGF after deceased-donor OLT and indirectly studied the sourcehepatic or extra-hepatic-of systemic oxidative stress in vivo in cirrhosis. We used a recently developed specific and sensitive mass spectrometry assay to measure 7␤-hydroxycholesterol and 7-ketocholesterol (oxysterols), markers of oxidative stress, in biological matrices. At univariate analysis, preoperative recipient 7␤-hydroxycholesterol plasma concentration was significantly higher in transplants with subsequent IPGF (n ‫؍‬ 9) compared with those with initial good graft function (IGGF; n ‫؍‬ 23) [mean ؎ SD: 30.63 ؎ 26.42 and 11.57 ؎ 15.76 ng/mL, respectively] (P ‫؍‬ 0.017). In a logistic regression model, which included also the Model for End-Stage Liver Disease (MELD) score, 7␤-hydroxycholesterol plasma concentration was an independent predictor of IPGF with an odds ratio of 1.17 (95% CI, 1.02-1.33, P ‫؍‬ 0.028). Patients with cirrhosis (n ‫؍‬ 32) had increased oxysterol plasma levels compared with healthy controls (n ‫؍‬ 49); livers with cirrhosis (n ‫؍‬ 21), however, had oxysterol content comparable with normal livers obtained from organ donors (n ‫؍‬ 19). Oxysterols persisted elevated in plasma 1 month after OLT (n ‫؍‬ 23). In conclusion, cirrhosis presents upregulated systemic oxidative stress likely of extrahepatic source that is associated with graft failure after OLT. (Liver Transpl 2005;11:1494-1504.)

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

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High preoperative recipient plasma 7β-hydroxycholesterol is associated with initial poor graft function after liver transplantation

et al. 2005

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“…Infection with HCV is associated with increased levels of ROS/RNS and decreased antioxidant levels in patients [71][72][73][74]. Patients infected with HCV show increases in lipid peroxidation levels in liver samples, serum, and peripheral blood mononuclear cells [72,[75][76][77][78][79][80].…”

Section: Viral Hepatitis and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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“…The effects of various antioxidants in plasma are additive, and the cooperation of antioxidants in human serum provides protection to an organism against attacks by free radicals 25–27. Determination of oxidants along with antioxidants is more useful in rendering information about the oxidant status of the organism,28 and that idea was followed in our research.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant defense and oxidative stress in children with acute hepatitis A

Popovic-Dragonjic¹,

Jovanović²,

Vrbić³

et al. 2011

Annals of Saudi Medicine

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BACKGROUND AND OBJECTIVES:Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients.DESIGN AND SETTING:Prospective, case-control study, over 2.5 years in patients under hospitalized and ambulatory care.PATIENTS AND METHODS:The levels of a whole-blood antioxidant, reduced glutathione; and plasma antioxidants, β-carotene, retinol, ascorbic acid, α-tocopherol; and the biomarker of oxidative stress, malondialdehyde, were evaluated in 50 pediatric patients (age range, 5-16 years; 29 males and 21 females) with acute hepatitis A and in 50 healthy children as control subjects (age range, 5-16 years; 25 males and 25 females).RESULTS:Plasma levels of reduced glutathione, β-carotene, retinol, α-tocopherol and ascorbic acid were significantly lower, while malondialdehyde plasma levels were significantly increased in the patient group when compared to the controls (P<.0001 for all parameters).CONCLUSIONS:Our findings show that pediatric patients with acute hepatitis A were influenced by oxidative stress, resulting in significantly lower levels of plasma antioxidants and increased lipid peroxidation. In the absence of other therapeutic options, antioxidant vitamin supplements could be added to the therapy for these patients to help reestablish the oxidant status balance. Further investigations to confirm this suggestion are recommended.

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Oxidative stress in chronic hepatitis C: not just a feature of late stage disease

Cited by 177 publications

References 46 publications

High preoperative recipient plasma 7β-hydroxycholesterol is associated with initial poor graft function after liver transplantation

High preoperative recipient plasma 7β-hydroxycholesterol is associated with initial poor graft function after liver transplantation

Role of free radicals in liver diseases

Antioxidant defense and oxidative stress in children with acute hepatitis A

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