Hepatic lipid peroxidation in vivo in rats with chronic iron overload.

Bacon, Bruce R.; Tavill, Anthony S.; Brittenham, Gary M.; Park, C H; Recknagel, Richard O.

doi:10.1172/jci110787

Cited by 385 publications

(160 citation statements)

References 30 publications

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“…23 Also, lipid peroxidation plays a role in the pathogenesis of hepatic injury Because aldehyde-protein adducts are immunogenic, 20 the presence of IgG autoantibodies to MDA lysine (using MDA-in an animal model of hepatic iron overload. 3 In the present study, we show evidence for enhanced lipid peroxidation low-density lipoprotein as an antigen for this assay) is indicative of oxidation-specific epitope generation. 20 Before treat-and expression of TGF-b1 in patients with GH, which are reversed by phlebotomy therapy.…”

Section: Discussionsupporting

confidence: 59%

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Excess iron induces hepatic oxidative stress and transforming growth factor β1 in genetic hemochromatosis

et al. 1997

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the absence of inflammation. TGF-b1 mediates many cellular Genetic hemochromatosis (GH) is associated with excess functions, including growth stimulation and inhibition, iron deposition in hepatocytes, which results in progressive apoptosis, increased extracellular matrix protein synthesis, hepatic injury. The pathogenesis of hepatic injury in GH is and decreased extracellular matrix degradation. [8][9][10][11][12] The colopoorly understood. In this study, we found enhanced oxidacalization of increased hepatic collagen a1(I) mRNA with tive stress in patients with GH, as evidenced by hepatic malon-TGF-b1 immunostaining suggests that TGF-b1 may also be dialdehyde (MDA)-protein adducts and by increased oxidaimportant in hepatic fibrogenesis associated with iron overtively modified serum proteins. MDA-lysine epitopes and load. The molecular mechanisms of TGF-b1 induction in oxidatively modified serum proteins, as well as immunogloburesponse to excess iron and enhanced lipid peroxidation in lin G autoantibodies against MDA-lysine epitopes, were inthe animal model of hemochromatosis are not known. creased in untreated GH patients and to a lesser extent in Iron directly or through the induction of cytokines, such GH heterozygotes compared with normal individuals. These as TGF-b1, could also play an important role in the developmarkers of ongoing oxidative stress decreased with phlebotment of liver injury 13-15 because excess iron removal in preomy treatment in GH patients. In addition, TGF-b1 colocalcirrhotic patients with GH prevents the development of fibroized with hepatic iron and MDA protein adducts in hepatosis and hepatocellular carcinoma formation. 16 However, it is cytes and sinusoidal cells of hepatic acinar zone 1 and not known whether excess hepatic iron in patients with GH normalized after iron removal. Our data suggest that iron is also associated with increased lipid peroxidation and TGFoverload increases both lipid peroxidation and TGF-b1 exb1 expression. In this study we analyzed whether hepatic pression, which together could promote hepatic injury and iron overload induces lipid peroxidation and TGF-b1 expresfibrogenesis. (HEPATOLOGY 1997;26:605-610.) sion in patients with GH. Genetic hemochromatosis (GH) is associated with excess PATIENTS AND METHODSiron deposition in hepatocytes, which results in hepatic injury. 1,2 The mechanisms responsible for the development of hydrazine to form a hydrazone complex, which was measured specof California, San Diego, CA; and 2 The Joint Liver Program, University of Queensland trophotometrically as described. 17 The hydrazone derivative has a

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Section: Discussionsupporting

confidence: 59%

“…GHstep by which excess iron causes cellular injury. [3][4][5] heterozygote status was assigned where there was one HLA haplo-…”

Section: Methodsmentioning

confidence: 99%

Excess iron induces hepatic oxidative stress and transforming growth factor β1 in genetic hemochromatosis

et al. 1997

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“…Free radicals catalyze the oxidation of protein and phospholipids (a process known as lipid peroxidation). Lipid peroxidation has 3 stages: initiation, propagation, and termination, and it leads to the formation of malondialdehyde, which can react with DNA bases to form DNA adducts, leading to the formation of DNA-DNA inter-strand crosslinks or DNA-protein crosslinks (Bacon et al 1983, Marnett 1999. Permanent modification of genetic material resulting from this "oxidative damage" represents the first step in mutagenesis, carcinogenesis, and ageing.…”

Section: Metal Ions In Cellsmentioning

confidence: 99%

Metal-on-metal hip resurfacing arthroplasty: A review of periprosthetic biological reactions

et al. 2008

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“…Reactive oxygen intermediates contributes to the pathogenesis of various hepatic disorders such as paracetamol intoxication, hemochromatosis, toxic hepatitis, and alcoholic liver injury [1][2][3][4] . Increased oxygen radical production leads to lipid peroxidation by induced cytochrome P4502E1 [5,6] .…”

Section: Introductionmentioning

confidence: 99%

N-acetylcysteine attenuates alcohol-induced oxidative stress in the rat

Özaras

Tahan²,

Aydın³

et al. 2003

WJG

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AIM:There is increasing evidence that alcohol-induced liver damage may be associated with increased oxidative stress. We aimed to investigate free-radical scavenger effect of nacetylcysteine in rats intragastrically fed with ethanol. METHODS:Twenty-four rats divided into three groups were fed with ethanol (6 g/kg/day, Group 1), ethanol and nacetylcysteine (1 g/kg, Group 2), or isocaloric dextrose (control group, Group 3) for 4 weeks. Then animals were sacrificed under ether anesthesia, intracardiac blood and liver tissues were obtained. Measurements were performed both in serum and in homogenized liver tissues. Malondialdehyde (MDA) level was measured by TBARS method. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were studied by commercial kits. Kruskal-Wallis test was used for statistical analysis. RESULTS:ALT and AST in Group 1 (154 U/L and 302 U/L, respectively) were higher than those in Group 2 (94 U/L and 155 U/L) and Group 3 (99 U/L and 168 U/L) (P=0.001 for both). Serum and tissue levels of MDA in Group 1 (1.84 nmol/ mL and 96 nmol/100 mg-protein) were higher than Group 2 (0.91 nmol/mL and 64 nmol/100 mg-protein) and Group 3 (0.94 nmol/mL and 49 nmol/100 mg-protein) (P<0.001 for both). On the other hand, serum GSH-Px level in Group 1 (8.21 U/g-Hb) was lower than Group 2 (16 U/g-Hb) and Group 3 (16 U/g-Hb) (P<0.001). Serum and liver tissue levels of SOD in Group 1 (11 U/mL and 26 U/100 mg-protein) were lower than Group 2 (18 U/mL and 60 U/100 mg-protein) and Group 3 (20 U/mL and 60 U/100 mg-protein) (P<0.001 for both). CONCLUSION:This study demonstrated that ethanolinduced liver damage is associated with oxidative stress, and co-administration of n-acetylcysteine attenuates this damage effectively in rat model. Ozaras R, Tahan V, Aydin S, Uzun H, Kaya S, Senturk H. Nacetylcysteine attenuates alcohol-induced oxidative stress in the rat. World J Gastroenterol 2003; 9(1): 125-128

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Hepatic lipid peroxidation in vivo in rats with chronic iron overload.

Cited by 385 publications

References 30 publications

Excess iron induces hepatic oxidative stress and transforming growth factor β1 in genetic hemochromatosis

Excess iron induces hepatic oxidative stress and transforming growth factor β1 in genetic hemochromatosis

Metal-on-metal hip resurfacing arthroplasty: A review of periprosthetic biological reactions

N-acetylcysteine attenuates alcohol-induced oxidative stress in the rat

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