Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former and has been suggested to be a relevant factor in aging as well as in different pathological conditions, such as heart attack, diabetes, and cancer. Ubiquinol is very sensitive against oxygen radicals and gives ubiquinone as an oxidation product. Therefore, the ratio of ubiquinol to ubiquinone should be a good marker of oxidative stress because of its definition. A method for the simultaneous detection of ubiquinol-10 and ubiquinone-10 in human plasma is described. Heparinized human plasma was mixed with 5 volumes of methanol and 10 volumes of hexane. After vigorous shaking and centrifugation, the hexane phase (5 microliters) was injected immediately and directly on to reverse-phase HPLC equipped with an on-line reduction column and an electrochemical detector in order to avoid the oxidation of ubiquinol to ubiquinone. It was found that the ratio of ubiquinol-10 to ubiquinone-10 was about 95/5 in human plasma from healthy donors. A significant increase in the oxidized form (ubiquinone-10) content was observed in plasmas of patients with hepatitis, cirrhosis, and hepatoma when compared with normal subjects, suggesting increased oxidative stress in these patients.
 ...
PMID:Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. 926 9

A recently discovered bacterium, Helicobacter hepaticus, infects the intrahepatic bile canaliculi of mice, causing a severe chronic hepatitis culminating in liver cancer. Thus, it affords an animal model for study of bacteria-associated tumorigenesis including H. pylori-related gastric cancer. Reactive oxygen species are often postulated to contribute to this process. We now report that hepatitis of male mice infected with H. hepaticus show significant increases in the oxidatively damaged DNA deoxynucleoside 8-hydroxydeoxyguanosine, with the degree of damage increasing with progression of the disease. Perfusion of infected livers with nitro blue tetrazolium revealed that superoxide was produced in the cytoplasm of hepatocytes, especially in association with plasmacytic infiltrates near portal triads. Contrary to expectations, Kupffer cells, macrophages, and neutrophils were rarely involved. However, levels of cytochrome P450 (CYP) isoforms 1A2 and 2A5 in hepatocytes appeared to be greatly increased, as indicated by the number of cells positive in immunohistochemistry and the intensity of staining in many cells, concomitant with severe hepatitis. The CYP2A5 immunohistochemical staining co-localized with formazan deposits resulting from nitro blue tetrazolium reduction and occurred in nuclei as well as cytoplasm. These findings suggest that CYP2A5 contributes to the superoxide production and 8-hydroxydeoxyguanosine formation, although reactive oxygen species from an unknown source in the hepatocytes leading to CYP2A5 induction or coincidental occurrence of these events are also possibilities. Three glutathione S-transferase isoforms, mGSTP1-1 (pi), mGSTA1-1 (YaYa), and mGSTA4-4, also showed striking increases evidencing major oxidative stress in these livers.
 ...
PMID:Increased oxidative DNA damage and hepatocyte overexpression of specific cytochrome P450 isoforms in hepatitis of mice infected with Helicobacter hepaticus. 932 26

Forty-five livers from conventionally slaughtered Holstein-Friesian steers with telangiectasis were studied by histochemical methods, immunolabelling for fibronectin, laminin and type IV collagen, and transmission electron microscopy. None of the previously described changes in telangiectasis (necrosis, hepatitis, thromboembolism, dilatation of the space of Disse by glycogen extruded from hepatocytes and reduced density of the perisinusoidal reticulin framework) were evident. Pretelangiectasis (sinusoidal dilatation) and telangiectasis (blood-filled cavities) were characterized by sinusoidal barrier alterations, leading to sinusoidal capillarization; and there was progressive formation of a true basement membrane and perisinusoidal fibrosis. Comparison of bovine liver telangiectasis and human peliosis hepatis suggests that they have a similar pathogenesis. It is suggested that a primary alteration of the sinusoidal barrier is responsible for an increased deposition of basement membrane components (fibronectin, laminin, type IV collagen) in the perisinusoidal region, and fibrosis. These are likely to render the exchange of oxygen and substrates between blood and hepatocytes more difficult and to produce haemodynamic imbalances, leading to hepatocyte atrophy and eventually to sinusoidal disruption.
 ...
PMID:Pretelangiectasis and telangiectasis of the bovine liver: a morphological, immunohistochemical and ultrastructural study. 974 55

Out of a prospective series of 142 consecutive episodes of hypoxic (ischemic) hepatitis (HH), we identified 17 episodes associated with an acute exacerbation of chronic respiratory failure (CRF) without left cardiac failure. In the aim to evaluate the role of arterial hypoxemia in the pathogenesis of HH associated with respiratory failure, these 17 episodes of HH (study group) were hemodynamically compared with a control group of 17 episodes of HH associated with congestive heart failure (CHF) (control group 1) and a group of 16 episodes of acute respiratory failure (ARF) not complicated by HH (control group 2). Arterial hypoxemia was significantly more severe in the study group (arterial blood tension in O2 [PaO2], 34 mm Hg) than in control group 1 (PaO2, 70 mm Hg; P <.0001) and control group 2 (PaO2, 45.5 mm Hg; P =.002). The role of arterial hypoxemia, however, appeared weakened by comparable degrees of systemic hypotension and liver passive congestion in episodes of HH associated with CRF and episodes of HH associated with CHF. Finally, the causative role of arterial hypoxemia emerged from hemodynamic measurements of cardiac index (CI), systemic vascular resistances (SVR), and oxygen transport: systemic hypotension in HH associated with CHF (control group 1) was the result of a fall in CI (median, 2. 33 L/min. m2; range, 1.21-3.14 L/min. m2) associated with high SVR (median, 2,492 dyn. s/cm5. m2; range, 1,382-4,053 dyn. s/cm5. m2), whereas in HH associated with respiratory failure (study group), systemic hypotension was the result of a fall in SVR (median, 1,053 dyn. s/cm5. m2; range, 646-3,148 dyn. s/cm5. m2), resulting in high CI (median, 4.23 L/min. m2; range, 1.9-5.32 L/min. m2) (P =.0087 and. 0038 for cardiac index and SVR, respectively). Moreover, measurements of oxygen transport in patients with HH associated with respiratory failure showed low values of O2 delivery (DO2) (median, 376 mL/min. m2; range, 253-427 mL/min. m2) as a result of extreme arterial hypoxemia despite high CI. In conclusion, these hemodynamic results and additional measurements of hepatic blood flow (HBF) by the method of galactose clearance at a low concentration suggest that in the setting of HH associated with respiratory failure, the liver is not "ischemic," despite hypotension, but rather "hypoxic" as a result of the combination of severe arterial hypoxemia and elevated central venous pressure (CVP).
 ...
PMID:Hypoxic hepatitis caused by acute exacerbation of chronic respiratory failure: a case-controlled, hemodynamic study of 17 consecutive cases. 991 19

Transgenic mice that express the viral coat proteins of hepatitis B virus (HBV) in the liver display hepatocellular damage, inflammation, regeneration, hyperplasia, and, eventually, neoplasia that is similar to that of people with chronic, active hepatitis caused by HBV infection. Hepatocellular regeneration, in the context of chronic injury and inflammation, is thought to expose dividing cells to excessive oxygen radicals, which are believed to lead to DNA damage and, ultimately, neoplasia. Because metallothioneins scavenge free radicals in vitro, we generated mice that express excess (>10-fold) metallothionein I (MT-I* mice) and the HBV surface antigens (HBsAg) to ascertain whether MT-I* would ameliorate aspects of the pathology induced by HBsAg. Markers of hepatocyte injury and tumorigenesis in HBsAg mice were compared to those in double transgenic (HBsAg and MT-I*) mice. Hepatic hyperplasia, histology, aneuploidy, and accumulation of an oxidative DNA adduct, 8-oxo-2'-deoxyguanosine, were examined. Although hepatitis and neoplasia were not prevented by MT-I* expression in the HBsAg mice, there was less hyperplasia and less aneuploidy. We conclude that MT-I produces a beneficial effect in this in vivo model of HBV-induced hepatitis.
 ...
PMID:Metallothionein overexpression suppresses hepatic hyperplasia induced by hepatitis B surface antigen. 1005 65

We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 microg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-alpha, but it partially prevented in vitro TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 microM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-alpha-dependent hepatic apoptosis.
 ...
PMID:Acteoside inhibits apoptosis in D-galactosamine and lipopolysaccharide-induced liver injury. 1042 28

Hepatitis C virus (HCV) is responsible for most cases of posttransfusion hepatitis and sporadic or community-acquired non-A, non-B hepatitis. Different generations of enzyme-linked immunosorbent assay have been generated for detecting antibodies to HCV epitopes. HCV-RNA quantitative analysis has been developed by means of polymerase chain reaction technique. This approach is the only reliable method for HCV-RNA tissue localization, being helpful in early diagnosis. HCV infected liver is characterized by an inflammatory infiltrate including CD4+, CD8+, and B lymphocytes. Evidence has been provided that in HCV patients CD8+ cell response is associated with low level of viraemia and higher level of disease activity. CD4+ T cells exhibit specificity for the core antigen, also correlating with disease activity and viraemia. Costimulatory molecules, cytokines, oxygen radicals, the complex Fas/Fas-ligand and soluble class I HLA structures are discussed as putative cofactors involved in disease evolution. Various forms of interferon (IFN)-alpha have been evaluated for the treatment of patients with HCV infection. Initial enthusiasm has been attenuated by the evidence of a low sustained virological response rate and the constant side effects of IFN-alpha therapy in patients with chronic HCV disease. Among possible markers for predicting therapeutic outcome in HCV-positive individuals, anti-core antibodies correlate positively with response to IFN-alpha administration, as well as reduction of interleukin-2 serum levels has been detected in patients with a good therapeutic response. Association between HCV infection and autoimmune phenomena, also in relation to IFN-alpha therapy has been reported. Finally, results of the combined treatment with IFN-alpha/ribavirin are illustrated.
 ...
PMID:Hepatitis C virus infection: immune responsiveness and interferon-alpha treatment. 1063 75

The Long-Evans Cinnamon (LEC) rat is a mutant strain of rats that accumulate copper (Cu) in the liver in much the same way as individuals who suffer from Wilson's disease (WD) and has been suggested as a model for this disease. Lipid peroxidation (LPO) is considered to be involved in the toxic action of Cu in the livers of LEC rats. We investigated the mechanism of LPO in the livers of LEC rats showing apparent signs of hepatitis. Several-fold higher LPO levels were observed in post-mitochondrial supernatant (S-9) fraction of livers from hepatitic LEC rats than in those from Wistar rats. To mimic living cells, we introduced NADPH-generating system (NADPH-gs) into the S-9 incubation system. Thus was ensured a constant supply of NADPH to vital enzymes that may be directly or indirectly involved in the generation and/or elimination of reactive oxygen species (ROSs), such as glutathione reductase (GSSG-R), which require NADPH for their reactions. The levels of LPO in liver S-9 from hepatitic LEC rats were further increased by incubating liver S-9 at 37 degrees C in the presence of NADPH-gs. This increase was inhibited by EDTA, butylated hydroxytoluene (BHT), and catalase (CAT), suggesting that some metal, most likely the accumulated Cu, and ROSs derived from hydrogen peroxide (H2O2) are involved in the increased levels of LPO in the livers of hepatitic LEC rats. The requirement of NADPH-gs for enhanced LPO in the livers of hepatitic LEC rats indicates the consumption of NADPH during reactions leading to LPO. It is known that H2O2, and consequently hydroxyl radical are generated during Cu-catalyzed glutathione (GSH) oxidation. The cyclic regeneration of GSH from GSSG by NADPH-dependent GSSG-R in the presence of NADPH-gs may cause sustained generation of hydroxyl radical in the presence of excess free Cu. The generation of H2O2 in S-9 fraction of livers from hepatitic LEC rats was observed to be significantly higher than that in S-9 fraction of livers from non-hepatitic LEC rats and Wistar rats. Moreover, in addition to the reported decrease in glutathione peroxidase (GPX) activity, we found that CAT activity was markedly decreased in LEC rats with hepatitis. The increased generation of H2O2 with reduced activities of GPX and CAT may result in cellular accumulation of H2O2 in the liver of hepatitic LEC rats. Taken altogether, it is suggested that the accumulated H2O2 undergoes the Fenton-type reaction with also accumulated free Cu, thus generating hydroxyl radical in the livers of hepatitic LEC rats and increasing LPO levels in these animals.
 ...
PMID:Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats. 1065 Sep 17

Many protein enzymes use general acid-base catalysis as a way to increase reaction rates. The amino acid histidine is optimized for this function because it has a pK(a) (where K(a) is the acid dissociation constant) near physiological pH. The RNA enzyme (ribozyme) from hepatitis delta virus catalyzes self-cleavage of a phosphodiester bond. Reactivity-pH profiles in monovalent or divalent cations, as well as distance to the leaving-group oxygen, implicate cytosine 75 (C75) of the ribozyme as the general acid and ribozyme-bound hydrated metal hydroxide as the general base in the self-cleavage reaction. Moreover, C75 has a pK(a) perturbed to neutrality, making it "histidine-like." Anticooperative interaction is observed between protonated C75 and a metal ion, which serves to modulate the pK(a) of C75. General acid-base catalysis expands the catalytic repertoire of RNA and may provide improved rate acceleration.
 ...
PMID:General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme. 1068 99

Mitochondria are involved in fatty acid beta-oxidation, the tricarboxylic acid cycle, and oxidative phosphorylation, which provide most of the cell energy. Mitochondria are also the main source of reactive oxygen species in the cell and are involved in cell demise through opening of the mitochondrial permeability transition pore. It was therefore to be expected that mitochondrial dysfunction could be a major mechanism of drug-induced liver disease. Microvesicular steatosis (which may cause liver failure, coma, and death) is the consequence of severe impairment of mitochondrial beta-oxidation. Endogenous compounds (such as cytokines or female sex hormones) or xenobiotics (including toxins such as ethanol and drugs such as aspirin, valproic acid, ibuprofen, or zidovudine) can inhibit beta-oxidation directly or through a primary effect on the mitochondrial genome or the respiratory chain itself. In some patients, infections and cytokines, or inborn errors of beta-oxidation enzymes or the mitochondrial genome, may favor the appearance of drug-induced microvesicular steatosis. Nonalcoholic steatohepatitis may develop under conditions causing prolonged, microvesicular, and/or macrovacuolar steatosis. In this condition, chronic impairment of mitochondrial beta-oxidation (causing steatosis) and the respiratory chain (increasing the production of ROS) lead to lipid peroxidation, which, in turn, may cause the diverse lesions of steatohepatitis, namely, necrosis, inflammation, Mallory's bodies, and fibrosis. Finally, mitochondria are involved in several forms of drug-induced cytolytic hepatitis, through inhibition or uncoupling of respiration or through a drug-induced or reactive metabolite-induced mitochondrial permeability transition. The latter effect commits hepatocytes to either apoptosis or necrosis, depending on the number of organelles that have undergone the permeability transition.
 ...
PMID:Hepatotoxicity due to mitochondrial dysfunction. 1081 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>