Comparative Study of the Effects of Atypical Antipsychotic Drugs on Plasma and Urine Biomarkers of Oxidative Stress in Schizophrenic Patients

非典型抗精神病药物对精神分裂症患者血浆和尿液氧化应激生物标志物影响的比较研究

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Abstract

PURPOSE: Evidence that antipsychotic drugs (ADs) can affect oxidative stress estimated with various biomarkers in schizophrenic patients is controversial and limited. Therefore, in the present study, we assessed the ability of six atypical ADs (clozapine, olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone) used in schizophrenia treatment to modulate oxidative damage to different biomolecules such as lipids and proteins. PATIENTS AND METHODS: We measured the levels of oxidative stress markers in plasma and urine: total antioxidant capacity by FRAP (according to a modified method of Benzie & Strain), thiobarbituric acid reactive species - TBARS (spectrophotometric method), 4-hydroxy-2-nonenal (4-HNE) (OxiSelect™ HNE Adduct Competitive ELISA Kit), 3-nitrotyrosine (3-NT) (OxiSelect™ Nitrotyrosine ELISA Kit) in plasma, and F2-isoprostanes (BIOXYTECH(®) Urinary 8-epi-Prostaglandin F2α) in the urine of 60 schizophrenic patients (before and after treatment) and in 30 healthy subjects. RESULTS: Our results showed that in schizophrenic patients levels of lipid peroxidation markers (TBARS, F2-isoprostanes) were higher than in healthy subjects but FRAP in schizophrenic patients was lower than in healthy controls and increased after 4-week treatment with tested ADs. A 4-week treatment with ADs caused the improvement of psychopathology symptoms estimated by Positive and Negative Syndrome Scale (PANSS) that was accompanied by decreased lipid peroxidation (F2-isoprostanes, TBARS; p=2.9x10(-6), p=7.6x10(-5), respectively) and an increase in total antioxidative capacity (FRAP) (p=5.16x10(-16)). CONCLUSION: Atypical antipsychotics especially clozapine, olanzapine and quetiapine demonstrate the effective outcome of antipsychotic treatment, beneficial antioxidative action by reducing lipid peroxidation and increased total plasma antioxidant activity.

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