{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:09:05Z","timestamp":1789528145733,"version":"build-2803163510"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1888,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Cell culture studies and animal models point to an important role of oxidative\/nitrosative stress in the pathogenesis of cerebral ammonia toxicity. However, it is unknown whether oxidative\/nitrosative stress in the brain is also characteristic of hepatic encephalopathy (HE) in humans. We therefore analyzed<\/jats:bold>\n                                 <jats:bold>\n                                    post mortem\n                                 <\/jats:bold>\n                                 <jats:bold>cortical brain tissue samples from patients with cirrhosis dying with or without HE in comparison with brains from patients without liver disease. Significantly elevated levels of protein tyrosine-nitrated proteins, heat shock protein-27, and 8-hydroxyguanosine as a marker for RNA oxidation were found in the cerebral cortex of HE patients, but not of patients with cirrhosis but without HE. Glutamine synthetase (GS) activity was significantly decreased, whereas GS protein expression was not significantly affected. Protein expression of the glutamate\/aspartate cotransporter was up-regulated in HE, whereas protein expression of neuronal and inducible nitric oxide synthases, manganese-dependent and copper\/zinc-dependent superoxide dismutase, and glial glutamate transporter-1 were not significantly increased.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>\n                                 <jats:bold>These data indicate that HE in patients with cirrhosis is associated with oxidative\/nitrosative stress, protein tyrosine nitration, and RNA oxidation, suggesting a role of oxidative stress in the pathogenesis of HE in patients with cirrhosis. Hepatology 2010<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23656","type":"journal-article","created":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T13:58:23Z","timestamp":1268056703000},"page":"256-265","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":135,"title":["Oxidative Stress Markers in the Brain of Patients With Cirrhosis and Hepatic Encephalopathy"],"prefix":"10.1097","volume":"52","author":[{"given":"Boris","family":"G\u00f6rg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Qvartskhava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-J\u00fcrgen","family":"Bidmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Palomero-Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Kircheis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Zilles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"H\u00e4ussinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R2-28-20250312","doi-asserted-by":"crossref","first-page":"14751480","DOI":"10.1016\/0016-5085(94)90552-5","article-title":"Proton magnetic resonance spectroscopy studies on human brain myoinositol in hypoosmolarity and hepatic encephalopathy.","volume":"107","author":"Haussinger","year":"1994","journal-title":"Gastroenterology"},{"key":"R3-28-20250312","doi-asserted-by":"crossref","first-page":"10351038","DOI":"10.1016\/S0168-8278(00)80110-5","article-title":"Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and lowgrade cerebral edema?","volume":"32","author":"Haussinger","year":"2000","journal-title":"J Hepatol"},{"key":"R4-28-20250312","doi-asserted-by":"crossref","first-page":"415429","DOI":"10.1023\/A:1021926405944","article-title":"1H magnetic resonance in the study of hepatic encephalopathy in humans.","volume":"17","author":"Cordoba","year":"2002","journal-title":"Metab Brain Dis"},{"key":"R5-28-20250312","doi-asserted-by":"crossref","first-page":"706717","DOI":"10.1016\/j.neuroimage.2008.02.057","article-title":"Quantitative cerebral water content mapping in hepatic encephalopathy.","volume":"41","author":"Shah","year":"2008","journal-title":"Neuroimage"},{"key":"R6-28-20250312","doi-asserted-by":"crossref","first-page":"833836","DOI":"10.1007\/BF00965694","article-title":"Ammoniainduced astrocyte swelling in primary culture.","volume":"16","author":"Norenberg","year":"1991","journal-title":"Neurochem Res"},{"key":"R7-28-20250312","first-page":"608618","article-title":"Simultaneous measurement of water volume and pH in single cells using BCECF and fluorescence imaging microscopy.","volume":"90","author":"AlvarezLeefmans","year":"2006","journal-title":"Biophys J"},{"key":"R8-28-20250312","doi-asserted-by":"crossref","first-page":"758771","DOI":"10.1002\/glia.20504","article-title":"Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured and vital brain slices.","volume":"55","author":"Reinehr","year":"2007","journal-title":"Glia"},{"key":"R9-28-20250312","doi-asserted-by":"crossref","first-page":"282288","DOI":"10.1002\/jnr.1222","article-title":"Ammoniainduced production of free radicals in primary cultures of rat astrocytes.","volume":"66","author":"Murthy","year":"2001","journal-title":"J Neurosci Res"},{"key":"R10-28-20250312","doi-asserted-by":"crossref","first-page":"739741","DOI":"10.1096\/fj.01-0862fje","article-title":"Ammonia induces MK801sensitive nitration and phosphorylation of protein tyrosine residues in rat.","volume":"16","author":"Schliess","year":"2002","journal-title":"FASEB J"},{"key":"R11-28-20250312","doi-asserted-by":"crossref","first-page":"11561165","DOI":"10.1136\/gut.2007.122176","article-title":"Pathogenetic mechanisms of hepatic encephalopathy.","volume":"57","author":"Haussinger","year":"2008","journal-title":"Gut"},{"key":"R12-28-20250312","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/glia.20019","article-title":"Hypoosmotic swelling increases protein tyrosine nitration in cultured rat astrocytes.","volume":"47","author":"Schliess","year":"2004","journal-title":"Glia"},{"key":"R13-28-20250312","doi-asserted-by":"crossref","first-page":"13631370","DOI":"10.1515\/BC.2006.171","article-title":"Pathogenetic interplay between osmotic and oxidative stress: the hepatic encephalopathy paradigm.","volume":"387","author":"Schliess","year":"2006","journal-title":"Biol Chem"},{"key":"R14-28-20250312","doi-asserted-by":"crossref","first-page":"7992","DOI":"10.1002\/glia.20737","article-title":"Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes.","volume":"57","author":"Kruczek","year":"2009","journal-title":"Glia"},{"key":"R15-28-20250312","doi-asserted-by":"crossref","first-page":"56779","DOI":"10.1002\/hep.22345","article-title":"Ammonia induces RNA oxidation in cultured astrocytes and brain in vivo.","volume":"48","author":"Gorg","year":"2008","journal-title":"Hepatology"},{"key":"R16-28-20250312","doi-asserted-by":"crossref","first-page":"587592","DOI":"10.1016\/S0959-4388(00)00128-8","article-title":"Local protein synthesis and its role in synapsespecific plasticity.","volume":"10","author":"Martin","year":"2000","journal-title":"Curr Opin Neurobiol"},{"key":"R17-28-20250312","doi-asserted-by":"crossref","first-page":"91719175","DOI":"10.1523\/JNEUROSCI.3040-05.2005","article-title":"Ribosome dysfunction is an early event in Alzheimers disease.","volume":"25","author":"Ding","year":"2005","journal-title":"J Neurosci"},{"key":"R18-28-20250312","doi-asserted-by":"crossref","first-page":"6671","DOI":"10.1073\/pnas.0609737104","article-title":"Oxidized messenger RNA induces translation errors.","volume":"104","author":"Tanaka","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"R19-28-20250312","doi-asserted-by":"crossref","first-page":"689692","DOI":"10.1212\/01.WNL.0000078816.05164.B1","article-title":"Miniasterixis in hepatic encephalopathy induced by pathologic thalamomotorcortical coupling.","volume":"61","author":"Timmermann","year":"2003","journal-title":"Neurology"},{"key":"R20-28-20250312","first-page":"291306","article-title":"Neurotransmitter receptor imbalances in motor cortex and basal ganglia in hepatic encephalopathy.","volume":"24","author":"PalomeroGallagher","year":"2009","journal-title":"Cell Physiol Biochem"},{"key":"R21-28-20250312","doi-asserted-by":"crossref","first-page":"8490","DOI":"10.1016\/j.febslet.2006.11.081","article-title":"Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration.","volume":"581","author":"Gorg","year":"2007","journal-title":"FEBS Lett"},{"key":"R22-28-20250312","doi-asserted-by":"crossref","first-page":"637644","DOI":"10.3109\/10715769709097867","article-title":"Superoxide production and antioxidant enzymes in ammonia intoxication in rats.","volume":"27","author":"Kosenko","year":"1997","journal-title":"Free Radic Res"},{"key":"R23-28-20250312","doi-asserted-by":"crossref","first-page":"21772186","DOI":"10.1152\/japplphysiol.01267.2001","article-title":"Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance.","volume":"92","author":"Kregel","year":"2002","journal-title":"J Appl Physiol"},{"key":"R24-28-20250312","doi-asserted-by":"crossref","first-page":"594604","DOI":"10.1111\/j.1365-2990.2006.00768.x","article-title":"The expression of nNOS, iNOS and nitrotyrosine is increased in the rat cerebral cortex in experimental hepatic encephalopathy.","volume":"32","author":"Suarez","year":"2006","journal-title":"Neuropathol Appl Neurobiol"},{"key":"R25-28-20250312","doi-asserted-by":"crossref","first-page":"10651073","DOI":"10.1002\/hep.20662","article-title":"Lipopolysaccharideinduced tyrosine nitration and inactivation of hepatic glutamine synthetase in the rat.","volume":"41","author":"Gorg","year":"2005","journal-title":"Hepatology"},{"key":"R26-28-20250312","doi-asserted-by":"crossref","first-page":"19261933","DOI":"10.1056\/NEJMoa050456","article-title":"Congenital glutamine deficiency with glutamine synthetase mutations.","volume":"353","author":"Haberle","year":"2005","journal-title":"N Engl J Med"},{"key":"R27-28-20250312","doi-asserted-by":"crossref","first-page":"207215","DOI":"10.1007\/BF01001062","article-title":"Regionselective reductions in activities of glutamine synthetase in rat brain following portacaval anastomosis.","volume":"8","author":"Girard","year":"1993","journal-title":"Metab Brain Dis"},{"key":"R28-28-20250312","doi-asserted-by":"crossref","first-page":"13691374","DOI":"10.1016\/S0891-5849(98)00339-6","article-title":"Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxication.","volume":"26","author":"Kosenko","year":"1999","journal-title":"Free Radic Biol Med"},{"key":"R29-28-20250312","doi-asserted-by":"crossref","first-page":"12371244","DOI":"10.1007\/BF02532401","article-title":"NMDA receptor antagonists prevent acute ammonia toxicity in mice.","volume":"21","author":"Hermenegildo","year":"1996","journal-title":"Neurochem Res"},{"key":"R30-28-20250312","doi-asserted-by":"crossref","first-page":"15831591","DOI":"10.1523\/JNEUROSCI.10-05-01583.1990","article-title":"Swellinginduced release of glutamate, aspartate, and taurine from astrocyte cultures.","volume":"10","author":"Kimelberg","year":"1990","journal-title":"J Neurosci"},{"key":"R31-28-20250312","doi-asserted-by":"crossref","first-page":"2093720944","DOI":"10.1074\/jbc.M412448200","article-title":"Acute insult of ammonia leads to calciumdependent glutamate release from cultured astrocytes, an effect of pH.","volume":"280","author":"Rose","year":"2005","journal-title":"J Biol Chem"},{"key":"R32-28-20250312","first-page":"6980","article-title":"Astrocytes as active participants of glutamatergic function and regulators of its homeostasis.","volume":"468","author":"Bezzi","year":"1999","journal-title":"Adv Exp Med Biol"},{"key":"R33-28-20250312","doi-asserted-by":"crossref","first-page":"293302","DOI":"10.1016\/S0006-8993(00)01993-4","article-title":"Modulation of glutamate transporters (GLAST, GLT1 and EAAC1) in the rat cerebellum following portocaval anastomosis.","volume":"859","author":"Suarez","year":"2000","journal-title":"Brain Res"},{"key":"R34-28-20250312","doi-asserted-by":"crossref","first-page":"876880","DOI":"10.1002\/hep.510300428","article-title":"Cerebral blood flow and the development of ammoniainduced brain edema in rats after portacaval anastomosis.","volume":"30","author":"Master","year":"1999","journal-title":"Hepatology"},{"key":"R35-28-20250312","doi-asserted-by":"crossref","first-page":"358366","DOI":"10.1016\/S0168-8278(01)00149-0","article-title":"Identification of osmosensitive and ammoniaregulated genes in rat astrocytes by Northern blotting and differential display reverse transcriptasepolymerase chain reaction.","volume":"35","author":"Warskulat","year":"2001","journal-title":"J Hepatol"},{"key":"R36-28-20250312","doi-asserted-by":"crossref","first-page":"730737","DOI":"10.1002\/jnr.10268","article-title":"GeneChip analysis shows altered mRNA expression of transcripts of neurotransmitter and signal transduction pathways in the cerebral cortex of portacaval shunted rats.","volume":"68","author":"Song","year":"2002","journal-title":"J Neurosci Res"},{"key":"R37-28-20250312","doi-asserted-by":"crossref","first-page":"1303813055","DOI":"10.1523\/JNEUROSCI.4407-08.2008","article-title":"Hsp27 protects against ischemic brain injury via attenuation of a novel stressresponse cascade upstream of mitochondrial cell death signaling.","volume":"28","author":"Stetler","year":"2008","journal-title":"J Neurosci"},{"key":"R38-28-20250312","doi-asserted-by":"crossref","first-page":"e4764","DOI":"10.1371\/journal.pone.0004764","article-title":"Identification of ischemic regions in a rat model of stroke.","volume":"4","author":"Popp","year":"2009","journal-title":"PLoS One"},{"key":"R39-28-20250312","doi-asserted-by":"crossref","first-page":"664672","DOI":"10.1097\/00005072-199706000-00004","article-title":"Multiple sclerosis: altered expression of 70 and 27kDa heat shock proteins in lesions and myelin.","volume":"56","author":"Aquino","year":"1997","journal-title":"J Neuropathol Exp Neurol"},{"key":"R40-28-20250312","doi-asserted-by":"crossref","first-page":"581588","DOI":"10.1080\/15216540600946456","article-title":"RNA damage and surveillance under oxidative stress.","volume":"58","author":"Li","year":"2006","journal-title":"IUBMB Life"},{"key":"R41-28-20250312","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1006\/abbi.1998.0755","article-title":"Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species.","volume":"356","author":"Ischiropoulos","year":"1998","journal-title":"Arch Biochem Biophys"},{"key":"R42-28-20250312","doi-asserted-by":"crossref","first-page":"17331748","DOI":"10.1111\/j.1528-1167.2008.01642.x","article-title":"Glutamine synthetase becomes nitrated and its activity is reduced during repetitive seizure activity in the pentylentetrazole model of epilepsy.","volume":"49","author":"Bidmon","year":"2008","journal-title":"Epilepsia"},{"key":"R43-28-20250312","doi-asserted-by":"crossref","first-page":"12871289","DOI":"10.1172\/JCI0215816","article-title":"Whence nitrotyrosine?","volume":"109","author":"Hurst","year":"2002","journal-title":"J Clin Invest"},{"key":"R44-28-20250312","first-page":"14401449","article-title":"Chronic hyperammonemia reduces the activity of neuronal nitric oxide synthase in cerebellum by altering its localization and increasing its phosphorylation by calciumcalmodulin kinase II.","volume":"106","author":"ElMlili","year":"2008","journal-title":"J Neurochem"},{"key":"R45-28-20250312","doi-asserted-by":"crossref","first-page":"879887","DOI":"10.1016\/j.neuroscience.2004.04.010","article-title":"Upregulation of endothelial nitric oxide synthase maintains nitric oxide production in the cerebellum of thioacetamide cirrhotic rats.","volume":"126","author":"Hernandez","year":"2004","journal-title":"Neuroscience"},{"key":"R46-28-20250312","doi-asserted-by":"crossref","first-page":"169172","DOI":"10.1016\/S0006-8993(97)00652-5","article-title":"Increased neuronal nitric oxide synthase expression in brain following portacaval anastomosis.","volume":"765","author":"Rao","year":"1997","journal-title":"Brain Res"},{"key":"R47-28-20250312","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.neulet.2004.06.046","article-title":"Fulminant hepatic failure induced oxidative stress in nonsynaptic mitochondria of cerebral cortex in rats.","volume":"368","author":"Reddy","year":"2004","journal-title":"Neurosci Lett"},{"key":"R48-28-20250312","doi-asserted-by":"crossref","first-page":"243248","DOI":"10.1016\/S0197-0186(00)00026-7","article-title":"Effects of ammonia on glutamate transporter (GLAST) protein and mRNA in cultured rat cortical astrocytes.","volume":"37","author":"Chan","year":"2000","journal-title":"Neurochem Int"},{"key":"R49-28-20250312","doi-asserted-by":"crossref","first-page":"145148","DOI":"10.1016\/S0304-3940(99)00816-2","article-title":"Ammonia downregulates GLAST mRNA glutamate transporter in rat astrocyte cultures.","volume":"276","author":"Zhou","year":"1999","journal-title":"Neurosci Lett"},{"key":"R50-28-20250312","doi-asserted-by":"crossref","first-page":"668677","DOI":"10.1007\/s00424-005-1499-y","article-title":"Impaired ability to increase water excretion in mice lacking the taurine transporter gene TAUT.","volume":"451","author":"Huang","year":"2006","journal-title":"Pflugers Arch"},{"key":"R51-28-20250312","doi-asserted-by":"crossref","first-page":"13821389","DOI":"10.1038\/ajg.2009.293","article-title":"Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with timedependent analysis.","volume":"104","author":"Guevara","year":"2009","journal-title":"Am J Gastroenterol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23656","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201007000-00028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T11:03:07Z","timestamp":1741777387000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201007000-00028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23656","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2010,7]]}}}