TY  - JOUR
AU  - Görg, B.
AU  - Qvartskhava, N.
AU  - Bidmon, H.-J.
AU  - Palomero-Gallagher, N.
AU  - Kircheis, G.
AU  - Zilles, K.
AU  - Häussinger, D.
TI  - Oxidative stress markers in the brain of patients with cirrhosis and hepatic encephalopathy
JO  - Hepatology
VL  - 52
SN  - 0270-9139
CY  - New York [u.a.]
PB  - Wiley Interscience
M1  - PreJuSER-10219
SP  - 256 - 265
PY  - 2010
N1  - This Study was Supported by Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 575 "Experimentelle Hepatologle" (Dusseldorf).
AB  - 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 post mortem 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. CONCLUSION: 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.
KW  - Adult
KW  - Aged
KW  - Amino Acid Transport System X-AG: analysis
KW  - Amino Acid Transport System X-AG: metabolism
KW  - Biological Markers: analysis
KW  - Biological Markers: metabolism
KW  - Cerebral Cortex: chemistry
KW  - Cerebral Cortex: metabolism
KW  - Excitatory Amino Acid Transporter 2: analysis
KW  - Excitatory Amino Acid Transporter 2: metabolism
KW  - Female
KW  - Glutamate-Ammonia Ligase: analysis
KW  - Glutamate-Ammonia Ligase: metabolism
KW  - Guanosine: analogs & derivatives
KW  - Guanosine: analysis
KW  - Guanosine: metabolism
KW  - HSP27 Heat-Shock Proteins: analysis
KW  - HSP27 Heat-Shock Proteins: metabolism
KW  - Hepatic Encephalopathy: etiology
KW  - Hepatic Encephalopathy: metabolism
KW  - Humans
KW  - Liver Cirrhosis: complications
KW  - Male
KW  - Middle Aged
KW  - Nitrates: analysis
KW  - Nitrates: metabolism
KW  - Oxidative Stress
KW  - RNA: analysis
KW  - RNA: metabolism
KW  - Tyrosine: analysis
KW  - Tyrosine: metabolism
KW  - Amino Acid Transport System X-AG (NLM Chemicals)
KW  - Biological Markers (NLM Chemicals)
KW  - Excitatory Amino Acid Transporter 2 (NLM Chemicals)
KW  - HSP27 Heat-Shock Proteins (NLM Chemicals)
KW  - Nitrates (NLM Chemicals)
KW  - Guanosine (NLM Chemicals)
KW  - 8-hydroxyguanosine (NLM Chemicals)
KW  - Tyrosine (NLM Chemicals)
KW  - RNA (NLM Chemicals)
KW  - Glutamate-Ammonia Ligase (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:20583283
C2  - pmc:PMC3395472
UR  - <Go to ISI:>//WOS:000279409200028
DO  - DOI:10.1002/hep.23656
UR  - https://juser.fz-juelich.de/record/10219
ER  -