[Role of oxidative stress in non-alcoholic steatohepatitis]. 2006

Hironori Mitsuyoshi, and Yoshito Itoh, and Takeshi Okanoue
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine.

Oxidative stress plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Reactive oxygen species (ROS) would derive from mitochondria, cytochrome P-450 2E1, peroxisome, and iron overload in the liver with steatosis. These excessive ROS is considered to cause simple steatosis to progress to NASH. On the other hand, oxidative stress exacerbates insulin sensitivity in hepatocytes, while hepatic steatosis causes oxidative stress. Thus, oxidative stress and insulin resistance might be interactive in NASH. Actually, we have found that the grade of steatosis correlates with serum thioredoxin level, a marker of oxidative stress, in NASH patients. Therefore, we propose that the feedback loop of oxidative stress, insulin resistance, and steatosis would play a significant role in the development of NASH.

UI MeSH Term Description Entries
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D005234 Fatty Liver Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS. Liver Steatosis,Steatohepatitis,Steatosis of Liver,Visceral Steatosis,Liver Steatoses,Liver, Fatty,Steatohepatitides,Steatoses, Liver,Steatoses, Visceral,Steatosis, Liver,Steatosis, Visceral,Visceral Steatoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D050356 Lipid Metabolism Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS. Metabolism, Lipid
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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