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)

BACKGROUND: The role of copper accumulation in the onset of hepatitis is still unclear. Therefore, we investigated a spontaneous disease model of primary copper-toxicosis in Doberman pinschers so to gain insights into the pathophysiology of copper toxicosis, namely on genes involved in copper metabolism and reactive oxygen species (ROS) defences. RESULTS: We used quantitative real-time PCR to determine differentially expressed genes within a target panel, investigating different groups ranging from copper-associated subclinical hepatitis (CASH) to a clinical chronic hepatitis with high hepatic copper concentrations (Doberman hepatitis, DH). Furthermore, a non-copper associated subclinical hepatitis group (N-CASH) with normal hepatic copper concentrations was added as a control. Most mRNA levels of proteins involved in copper binding, transport, and excretion were around control values in the N-CASH and CASH group. In contrast, many of these (including ATP7A, ATP7B, ceruloplasmin, and metallothionein) were significantly reduced in the DH group. Measurements on defences against oxidative stress showed a decrease in gene-expression of superoxide dismutase 1 and catalase in both groups with high copper. Moreover, the anti-oxidative glutathione molecule was clearly reduced in the DH group. CONCLUSION: In the DH group the expression of gene products involved in copper efflux was significantly reduced, which might explain the high hepatic copper levels in this disease. ROS defences were most likely impaired in the CASH and DH group. Overall, this study describes a new variant of primary copper toxicosis and could provide a molecular basis for equating future treatments in dog and in man.
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PMID:Differential expression of copper-associated and oxidative stress related proteins in a new variant of copper toxicosis in Doberman pinschers. 1579 Apr 12

The present study was aimed to examine the protective effects of Sargassum polycystum (Phaeophyceae) alcoholic extract on changes in liver mitochondrial enzymes against acetaminophen induced toxic hepatitis in experimental rats. The levels of protein, lipid peroxide, glutathione (GSH) in mitochondrial fraction, superoxide dismutase (SOD) and catalase (CAT) were also determined. The activities of tricarboxylic acid enzymes such as isocitrate dehydrogenase (ICD), alpha-ketoglutarate dehydrogenase (alpha-KGD), succinate dehydrogenase (SD), malate dehydrogenase (MD), NADH dehydrogenase, and cytochrome-c-oxidase were determined in mitochondrial fraction. The rats intoxicated with acetaminophen showed significant elevation in the levels of lipid peroxides with decreased levels of protein, GSH, SOD, CAT and impaired tricarboxylic acid cycle enzyme activities. The prior oral administration of S. polycystum alcoholic extract showed significant diminution in the severity of toxic hepatitis in acetaminophen-induced rats by maintaining the activities of tricarboxylic acid enzymes with concomitant improvement in the hepatic mitochondrial antiperoxidative status when compared with intoxicated animals. The results obtained in the present study indicate that the protective effects of S. polycystum extract may be due to the presence of some active compounds that are inhibitory against the free radicals generated during lipid peroxidation in acetaminophen induced toxic hepatitis.
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PMID:Antioxidant effect of Sargassum polycystum (Phaeophyceae) against acetaminophen induced changes in hepatic mitochondrial enzymes during toxic hepatitis. 1616 51

Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. Male LEC rats were given a single subcutaneous injection of 300 mg/kg of GalN or vehicle (0.9% NaCl) at 14 weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2'-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12 weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate.
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PMID:Prevention of lethal hepatic injury in Long-Evans Cinnamon (LEC) rats by D-galactosamine hydrochloride. 1653 99

Biochemiluminiscense parameters (light sum and maximum flash) show that free radical oxidation intensity (increased in serum blood of rats with toxic hepatitis) is decreased upon the treatment with melatonin. At the same time, the tg a2 value (reflecting the total antioxidant activity) changes toward the normal level, which indicated a decrease in the degree of antioxidant system mobilization. Superoxide dismutase and catalase activities (increased in the liver and blood serum of rats with toxic hepatitis) also showed the tendency to decrease upon the melatonin administration. Evidently, melatonin can act as a factor correcting the oxidative stress caused by the toxic damage of liver.
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PMID:[Melatonin as a corrector of free radical oxidation processes during toxic damage of liver in rat]. 1740 93

Murine hepatic cytochrome P450 2A5 (CYP2A5), unlike most CYP enzymes, is upregulated during hepatitis and hepatotoxic conditions, but the common stimulus for its induction remains unknown. We investigated the involvement of oxidative stress in the regulation of CYP2A5 expression using an oxidative stress-sensitive glucose-6-phosphate dehydrogenase (G6PD)-deficient mouse model. Treatment of deficient and wild-type mice with the prototypical CYP2A5-inducer pyrazole for 72h led to a significantly greater degree of induction of CYP2A5 mRNA, protein and activity in deficient mice, with the greatest increase observed in animals homozygous for the deficiency. However, markers of oxidative stress including protein carbonyl, 8-hydroxydeoxyguanosine, malondiadehyde and 4-hydroxyalkenal levels were unaltered with pyrazole treatment. Furthermore, CYP2A5 expression was not altered in G6PD-deficient mice treated with the pro-oxidant menadione whereas DNA, lipid, and protein markers of oxidative stress were significantly increased. The antioxidant polyethylene glycol-conjugated catalase, while decreasing oxidative stress in menadione-treated mice, did not prevent the induction of CYP2A5 by pyrazole. Finally, the ER stress marker protein, GRP78, was increased following pyrazole treatment in G6PD-deficient compared to wild-type mice. These findings do not support a central role for generalized cellular oxidative stress in the regulation of CYP2A5 and suggest that additional factors related to G6PD-deficiency, such as ER stress, may be involved.
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PMID:Expression of cytochrome P450 2A5 in a glucose-6-phosphate dehydrogenase-deficient mouse model of oxidative stress. 1806 88

Oxidative stress, cytokine over expression and Kupffer cell activation are well-documented pathological factors in the development of alcoholic liver disease. Bicyclol is a novel synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory property. The present study was to investigate the effect of bicyclol on acute alcohol-induced liver injury and related mechanisms in mice. Bicyclol (200, 300 mg/kg) was given to mice by gavage for three times. Alcohol (6 g/kg) was administered orally 1 h after the last dose of bicyclol. All animals were sacrificed at different time points after alcohol administration. Liver injury was evaluated by biochemical and histopathological examination. Lipid peroxidation and the activity of antioxidants were measured by spectrophotometric method. Expression of cytokines and CD14 were determined by enzyme-linked immunosorbent assay, reverse transcriptional-polymerase chain reaction and immunohistochemical staining. As a result, bicyclol pretreatment significantly protected against acute alcohol-induced liver injury as evidenced by the decrease of elevated serum alanine aminotransferase and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated the formation of thiobarbituric acid-reactive substance and restored impaired antioxidants, including glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Over-expression of cytokines, such as tumor necrosis factor alpha and interleukin 1beta, elevated plasma endotoxin level, and up-regulation of CD14 were also suppressed by bicyclol in alcohol-intoxicated mice. The protective effect of bicyclol on alcohol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the cytokine expression at both protein and gene level, and inhibit the activation of Kupffer cells by decreasing plasma endotoxin level and CD14 expression.
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PMID:Protective effect of bicyclol on acute alcohol-induced liver injury in mice. 1837 52

The authors have studied hepatoprotective actions of new derivatives of 3-hydroxipyridine on an experimental model of toxic hepatitis (140 white mice). Mexidol and berlithion are choosed as the preparations of comparison. The method of light microscopy is used for the exploration of morphological changes. The cytolytic contents activity, catalase activity and the level of MDA have been determined in blood serum. The antitoxic effect is valued by the survival of the animals. It is found that all examined bonds is corrected morphological changes in toxic hepatitis and increased the index of animals survival, which is more expressed than the preparations of comparison.
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PMID:[Study of hepatoprotective activity of ethylmethylhydroxypyridine fumarate and lipoate in the experimental toxic hepatitis]. 1841 6

To elucidate the pathophysiological significance of adenosine 3'-monophosphate (3'-AMP) forming enzyme in mice, the effect of streptozotocin (STZ) on the enzyme activities and adenine nucleotide levels in the ICR mice (4-week-old) liver was examined. After 2 weeks, treatment with a single dosage of STZ (100, 150 or 200 mg/kg i.p.) induced a dose-dependent hyperglycemia and hypoinsulinemia but had no effect on serum alanine aminotransferase activity, indicating that STZ generated type 1 diabetes without hepatitis. In the diabetic liver, the activities of superoxide dismutase (SOD), catalase and ATP levels decreased, and the microsomal CYP2E1 activity increased. Changes of these biological activities might disrupt the cellular homeostatic balance of reactive oxygen species (ROS) production. The activities of 3'-AMP forming enzyme, one of the ribonucleases, in hepatic homogenates were not altered. However, in the STZ 200 mg/kg group, the cytosolic forming enzyme activities were enhanced, and inversely, the mitochondrial activity was reduced significantly, indicating that the decrease in the mitochondrial activity may be accelerated by development of diabetes due to the decrease in the antioxidant defense system and/or increase in ROS production. With the decrease in the 3'-AMP forming enzyme activity, the levels of 3'-AMP, a P-site inhibitor of adenylate cyclase, in mitochondrial were significantly reduced. These results obtained suggested that change in the mitochondrial 3'-AMP forming enzyme activity might reflect the pathophysiological change of mitochondrial function with the development of diabetes. Our results also suggested that change in cytosolic enzyme activity might serve as a new biomarker of oxidative stress because significant negative correlation between the activities of cytosolic 3'-AMP forming enzyme and SOD was found in the early stage of diabetes.
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PMID:Hepatic changes in adenine nucleotide levels and adenosine 3'-monophosphate forming enzyme in streptozotocin-induced diabetic mice. 1854 12

Injection of D-galactosamine and lipopolysaccharide (DGaIN/LPS) is useful as an experimental model of acute hepatic damage. Juvenile rats were used for investigation. The hepatoprotective activity of aqueous garlic (Allium sativum) extract (AGE) at a dose of 300 mg/kg body weight for 14 days, intraperitoneal (i.p.) prior to the induction of DGalN/LPS, was investigated against DGalN/LPS-induced hepatitis in rats. DGalN/LPS (300 mg/kg body weight/30 microg/kg body weight, i.p.), induced hepatic damage that was manifested by a significant increase in the activities of marker enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (gamma GT)], bilirubin, lipid peroxides (LPO), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) activity level in serum. Also, the lipid profile in serum and liver homogenate including total cholesterol, triglycerides, free fatty acids and phospholipids were significantly deteriorated. The antioxidant enzyme activities (superoxide dismutase, SOD; reduced glutathione, GSH; catalase, CAT and glutathione peroxidase, GPX) in liver homogenate were significantly decreased in the DGalN/LPS. Pretreatment of rats with AGE reversed these altered parameters near to normal control values. Results of this study revealed that AGE could afford a significant protection in the alleviation of DGalN/LPS-induced hepatic damage.
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PMID:Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipoploysaccharide in rats. 1857 Feb 25

Human hepatocellular carcinoma (HCC) is one of the commonest causes of mortality among solid organ malignancies. The incidence of HCC in the United States is rising. Few proteomic biomarker studies have been done in U.S. populations. Tumor and nonmalignant tissue from three American patients with hepatitis and non-hepatitis-associated HCC were analyzed to find common differences in protein expression. Proteins were separated by 2D electrophoresis (isoelectric focusing followed by 10% SDS-PAGE). Gels were fixed and then stained with Coomassie brilliant blue. Digitization and processing were performed using the PDQuest software. The Student's t-test was used to detect quantitative protein changes between tumor and nonmalignant liver consistent in all sample pairs with a cutoff made at P < 0.01. This yielded a total of 20 spots with significant (>2 fold) abundance changes. Matrix-assisted laser desorption ionization mass spectrometry analysis was performed using Waters Micomass M@LDI SYSTEM. The proteins were then identified using manual ProFound. Among the 20 spots, 10 showed overexpression and 10 showed underexpression in tumor. Overexpressed proteins included beta-5-tubulin, beta-actin, vimentin, hypermethylated in cancer 2 protein, heat-shock 70-kDa protein 9B, serum albumin, 39S ribosomal protein L45, butyrophilin, autoimmune regulator, and transcription factor ETV7. Underexpressed proteins included BiP protein, superoxide dismutase, peroxiredoxin 2, inoraganic pyrophosphatase, keratin 8, carbonic anhydrase 1, repulsive guidance molecule, catalase, C-1-tetrahydrofolate synthase, and hemoglobin alpha-2. Of particular interest, the protein autoimmune regulator was expressed 14-fold higher in tumor tissue, suggesting it may have a role in HCC. Validation and further investigation of these protein changes may lead to the discovery of new molecular targets for therapy, biomarkers for early detection, and new endpoints for therapeutic efficacy and toxicity.
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PMID:A pilot study of proteomic profiles of human hepatocellular carcinoma in the United States. 1953 95


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