title: Is cognitive impairment in cirrhotic patients due to increased peroxynitrite and oxidative stress?
abstract: Cirrhotic patients may suffer minimal hepatic encephalopathy (MHE), with mild cognitive impairment. 3-Nitro-tyrosine levels are a good biomarker for diagnosis of the cognitive impairment and MHE in cirrhotic patients. This suggests that oxidative stress could be involved in the induction of cognitive and motor alterations in MHE. We have observed that patients with MHE show increased oxidative stress in blood compared with cirrhotic patients without MHE, with increased lipid peroxidation, DNA oxidation, protein carbonylation, 3-nitrotyrosine, oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio, and GSH levels. The activities of antioxidant enzymes are enhanced in erythrocytes and mononuclear cells from patients with and without MHE compared with control subjects. Only glutathione peroxidase activity was increased in MHE patients compared with patients without MHE. Oxidative stress markers in blood, especially GSSG/GSH ratio, GSH, malondialdehyde, and 3-nitrotyrosine, correlate with deficits in attention and motor coordination. The increase in antioxidant activities in patients would be an adaptive mechanism to cope with enhanced oxidative stress, although it is not effective enough to normalize it. Our observations lead to the hypothesis that oxidative stress and increased peroxynitrite formation would mediate the synergistic effects of hyperammonemia and inflammation on cognitive and motor impairment in MHE.
authors.affiliation: 1 Laboratorio de Neurobiología , Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain .
authors.forename: Carla
authors.initials: C
authors.lastname: Gimenez-Garzó
authors.forename: Amparo
authors.initials: A
authors.lastname: Urios
authors.forename: Ana
authors.initials: A
authors.lastname: Agustí
authors.forename: Olga
authors.initials: O
authors.lastname: González-López
authors.forename: Desamparados
authors.initials: D
authors.lastname: Escudero-García
authors.forename: Amparo
authors.initials: A
authors.lastname: Escudero-Sanchis
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Serra
authors.forename: Remedios
authors.initials: R
authors.lastname: Giner-Durán
authors.forename: Carmina
authors.initials: C
authors.lastname: Montoliu
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
mesh_terms: D000368:Aged; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000378:metabolism*
chemical_list: D030421:Peroxynitrous Acid