Activities of free oxygen radical scavenger enzymes in human liver

Togashi, Hitoshi; Shinzawa, Haruhide; Wakabayashi, Hiroto; Nakamura, Toichiro; Yamada, Nobuo; Takahashi, Tsuneo; Ishikawa, Makoto

doi:10.1016/0168-8278(90)90114-7

Cited by 44 publications

(23 citation statements)

References 25 publications

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“…The observation that GCDC rapidly generates intracellular ROS in a dosedependent manner led us to exam whether or not the antioxidant levels change. Cu/Zn-SOD, catalase and other antioxidants have been reported to be lowered in a diseased human liver [8], and in the liver of BDL rats [9]. They suggested that the reduction in the hepatic antioxidant defense system, such as SOD and catalase, could contribute to the development of liver injury through an Chu/Lee-Kang/Lee/Lee enhancement of hepatic lipid peroxidation.…”

Section: Antioxidants Levels For Sod Catalase Prx I and Prx Iimentioning

confidence: 99%

“…Recently, several ROS scavenging enzymes, such as Cu, Zn superoxide dismutase (SOD), catalase, or glutathione (GSH) have been reported to be lower in a diseased liver of human or bile duct-ligand (BDL) rats, therefore increasing the susceptibility of the liver to ROS injury [8,9]. In addition, ·-tocopherol or SOD addition significantly inhibited the hydrophobic bile acid-induced LPO and injury in isolated hepatocytes and the liver [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Roles of Reactive Oxygen Species, NF-κB, and Peroxiredoxins in Glycochenodeoxycholic Acid-Induced Rat Hepatocytes Death

Chu

Lee-Kang²,

Lee

et al. 2003

Pharmacology

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The aim of this study was to determine the roles of reactive oxygen species (ROS), NF-ĸB and antioxidants in glycochenodeoxycholic acid (GCDC, 0–400 µmol/l, 0.5– 3 h)-induced hepatocytes death. The differential uptake of ethidium bromide and acridine orange revealed that apoptotic death occurred dose-dependently in GCDC-treated hepatocytes whereas necrotic death was prominent especially at higher GCDC concentrations (≧200 µmol/l). ROS generation measured fluorometrically either by a confocal laser microscope or by a microplate fluorescence reader was increased dose-dependently. The dose-dependent NF-ĸB activation with the significant IĸB-α decrease preceded both hepatocyte cell death and the alteration of antioxidant enzymes. The Cu/Zn-SOD level among several antioxidants, we checked, remained unchanged. In contrast, the catalase level and its enzymatic activity were markedly decreased only at 400 µmol/l. The Prx I and Prx II, newly defined antioxidant enzymes reducing H₂O₂ levels were decreased at the 200 and 400 µmol/l. These observations point to ROS generation in the GCDC-treated hepatocyte as the proximate event that triggers NF-ĸB activation, IĸB-α proteolysis, Prx depletion, and finally cell death. And oxidative stress may be more related to necrotic cell death in GCDC-treated hepatocytes.

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Section: Antioxidants Levels For Sod Catalase Prx I and Prx Iimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of Reactive Oxygen Species, NF-κB, and Peroxiredoxins in Glycochenodeoxycholic Acid-Induced Rat Hepatocytes Death

Chu

Lee-Kang²,

Lee

et al. 2003

Pharmacology

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“…Chronic alcohol abuse results in a variety of pathological effects, including damage to the liver and other organs and is associated with an increased risk of certain types of cancers and results in patho-physiological conditions in various organs of the human body. The available literature also suggests that increase in oxidative stress has been linked with genotoxicity which has played instrumental role in the pathogenesis of liver related disease and fibrosis [3,4,5,6].…”

Section: Introductionmentioning

confidence: 99%

Effect of Alcohol Consumption and Oxidative Stress and Its Role in DNA Damage

Deshpande¹,

Kandi²,

Muddeshwar³

et al. 2014

AJBR

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Oxidative stress has been increasingly implicated in different stages of liver cirrhosis and has been found responsible for DNA damage. Alcohol consumption and oxidative stress have been linked with DNA damage and progression of disease, leading to the hypothesis that chronic alcoholism causes DNA damage. The study was aimed at evaluating the relation between alcohol consumption and relative oxidative damage in different stages of liver cirrhosis. The study included two groups based on severity of cirrhosis of liver; categorized as compensated and decompensated liver cirrhotic patients based on child Pugh criteria. All decompensated cirrhotic patients in the study group had significantly higher MDA levels (P < 0.001) associated with DNA Damage (P > 0.01) than those with compensated cirrhotic patients and control group who were not suffering from liver cirrhosis. These results highlighted a significant higher degree of DNA damage in decompensated cirrhotic patients associated with oxidative stress as shown from greater average DNA migration in decompensated cirrhotic patients than in the compensated cirrhotic patients with low level of oxidative stress. Thus these results suggest that increase in MDA levels may be associated with pathogenesis and progression of liver cirrhosis.

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“…Recent studies have suggested that oxidant stress may play an important role in the pathogenesis of hepatic injury during cholestasis (6,(12)(13)(14)(15)(16). Supporting this proposed mechanism is the observation that ␣-tocopherol, the major membraneassociated, lipid-soluble antioxidant, reduces both the generation of ROS and injury to hepatocytes exposed to hydrophobic bile acids (17,18) and in the intact rat infused with bile acids (6).…”

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confidence: 99%

Role of Oxidant Stress in the Permeability Transition Induced in Rat Hepatic Mitochondria by Hydrophobic Bile Acids

et al. 2001

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Hydrophobic bile acids may cause hepatocellular necrosis and apoptosis during cholestatic liver diseases. The mechanism for this injury may involve mitochondrial dysfunction and the generation of oxidant stress. The purpose of this study was to determine the relationship of oxidant stress and the mitochondrial membrane permeability transition (MMPT) in hepatocyte necrosis induced by bile acids. The MMPT was measured spectrophotometrically and morphologically in rat liver mitochondria exposed to glycochenodeoxycholic acid (GCDC). Freshly isolated rat hepatocytes were exposed to GCDC and hepatocellular necrosis was assessed by lactate dehydrogenase release, hydroperoxide generation by dichlorofluorescein fluorescence, and the MMPT in cells by JC1 and tetramethylrhodamine methylester fluorescence on flow cytometry. GCDC induced the MMPT in a dose-and Ca 2ϩ -dependent manner. Antioxidants significantly inhibited the GCDC-induced MMPT and the generation of hydroperoxides in isolated mitochondria. Other detergents failed to induce the MMPT and a calpain-like protease inhibitor had no effect on the GCDC-induced MMPT. In isolated rat hepatocytes, GCDC induced the MMPT, which was inhibited by antioxidants. Blocking the MMPT in hepatocytes reduced hepatocyte necrosis and oxidant stress caused by GCDC. Oxidant stress, and not detergent effects or the stimulation of calpain-like proteases, mediates the GCDC-induced MMPT in hepatocytes. We propose that reducing mitochondrial generation of reactive oxygen species or preventing increases in mitochondrial Ca 2ϩ may protect the hepatocyte against bile acid-induced necrosis. 1-3). Although hydrophobic bile acids cause injury to isolated hepatocytes (4), cultured hepatocytes (5), and the intact liver (6), the mechanisms of this toxicity are not fully understood. Both hepatocellular necrosis at higher bile acid concentrations (4) and apoptosis at lower concentrations (7) have been demonstrated and are proposed as playing a role in cholestatic liver injury. Hepatocyte necrosis is characterized by cellular swelling, loss of mitochondrial respiratory function, depleted cellular ATP levels, and formation of plasma membrane blebs that rupture and release cellular contents (8, 9). In cholestatic liver ABSTRACT519

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Activities of free oxygen radical scavenger enzymes in human liver

Cited by 44 publications

References 25 publications

Roles of Reactive Oxygen Species, NF-κB, and Peroxiredoxins in Glycochenodeoxycholic Acid-Induced Rat Hepatocytes Death

Roles of Reactive Oxygen Species, NF-κB, and Peroxiredoxins in Glycochenodeoxycholic Acid-Induced Rat Hepatocytes Death

Effect of Alcohol Consumption and Oxidative Stress and Its Role in DNA Damage

Role of Oxidant Stress in the Permeability Transition Induced in Rat Hepatic Mitochondria by Hydrophobic Bile Acids

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