Oxidative/Nitrative Modifications of Plasma Proteins and Thiols from Patients with Schizophrenia

Abstract

Objective: The level of various specific biomarkers of oxidative stress in plasma from schizophrenic patients, as well as biomarkers (the level of isoprostanes) in urine in schizophrenic patients was described. The aim of our present study was to evaluate biomarkers of oxidative stress by oxidative/nitrative modifications of plasma proteins (by measuring the level of carbonyl groups and 3-nitrotyrosine in proteins) from patients with schizophrenic disorders and from control group. We also investigated the level of low-molecular-weight thiols [glutathione (GSH), cysteine (CSH), cysteinylglycine (CGSH) and homocysteine] in plasma obtained from schizophrenic patients and from healthy volunteers. Patients hospitalized in the 1st and 2nd Psychiatric Department of the Medical University in Lodz, Poland were interviewed with a special questionnaire (treatment, course of diseases, dyskinesis and other extrapyramidal syndromes). According to DSM-IV criteria, all patients had a diagnosis of paranoid type. They were treated with antipsychotic drugs (clozapine, risperidone, olanzapine). The mean duration of schizophrenia was about 5 years. Methods: Levels of carbonyl groups and 3-nitrotyrosine residues in plasma proteins were measured by ELISA and a competition ELISA, respectively. High-performance liquid chromatography was used to analyze free thiols in plasma. Results: We observed a statistically increased level of biomarkers of oxidative/nitrative stress such as carbonyl groups or 3-nitrotyrosine in plasma proteins from schizophrenic patients. In schizophrenic patients the amount of homocysteine in plasma was higher compared with the control group; the level of GSH, CSH and CGSH was decreased. This indicates that reactive oxygen species and reactive nitrogen species may stimulate oxidative/nitrative modifications of plasma proteins in schizophrenic patients. Conclusion: Considering the data presented in this study, we suggest that the amount of carbonyl groups and 3-nitrotyrosine in plasma proteins may be important indicators of protein damage in vivo in schizophrenia.

Status of antioxidant defense and lipid peroxidation in schizophrenics with positive, negative and cognitive symptoms

“…The enzyme GSH-Px then regenerates GSH from GSSG with NADPH as a source of hydrogen. In the present study erythrocyte GSH concentration and the activity of GSH-Px were significantly reduced in shizophrenic subjects with the three major symptoms, this was in agreement with recent studies 12,13,15,30 in which they reported decreased activity of GSH-Px in schizophrenic patients; likewise, other researchers 35,38,39 reported reduction in concentration GSH in their studies. CAT activity is one of the most important mechanisms by which RBC dispose of H 2 O 2 produce by dismutation reaction of O 2 in a cell.…”

Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism

“…Clinical trials demonstrated increased total plasma peroxide [89] and serum NO levels in schizophrenic patients [90]. The increased levels of plasma MDA [89,[91][92][93][94], thiobarbituric acid reactive substances (TBARS) [95] and isoprostanes in urine [95], higher levels of 3-nitrotyrosine in plasma [96] and increased DNA [97,98] and RNA damage [98] were also observed.…”

Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol

“…Schizophrenia is also associated with oxidative/nitrative stress [2][3][4][5][6][7][8][9][10][11][12][13]. Moreover, in schizophrenia, oxidative stress may be induced by treatment of antipsychotic drugs [14,15].…”