Dietrich-Muszalska Anna, Kolodziejczyk-Czepas Joanna, Nowak Pawel
Medical University of Lodz, Department of Biological Psychiatry and Neurophysiology, Lodz, Poland.
University of Lodz, Department of General Biochemistry, Lodz, Poland.
Neuropsychiatr Dis Treat. 2021 Feb 17;17:555-565. doi: 10.2147/NDT.S283395. eCollection 2021.
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.
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.
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, p=7.6x10, respectively) and an increase in total antioxidative capacity (FRAP) (p=5.16x10).
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.
抗精神病药物(ADs)能否影响精神分裂症患者中通过多种生物标志物评估的氧化应激,相关证据存在争议且有限。因此,在本研究中,我们评估了用于精神分裂症治疗的六种非典型抗精神病药物(氯氮平、奥氮平、喹硫平、利培酮、阿立哌唑和齐拉西酮)调节对不同生物分子(如脂质和蛋白质)氧化损伤的能力。
我们测量了血浆和尿液中的氧化应激标志物水平:通过FRAP法(根据Benzie和Strain的改良方法)测定总抗氧化能力,采用分光光度法测定硫代巴比妥酸反应性物质(TBARS),使用OxiSelect™ HNE加合物竞争ELISA试剂盒测定4-羟基-2-壬烯醛(4-HNE),使用OxiSelect™ 硝基酪氨酸ELISA试剂盒测定血浆中的3-硝基酪氨酸(3-NT),并使用BIOXYTECH尿8-表前列腺素F2α试剂盒测定60例精神分裂症患者(治疗前后)及30名健康受试者尿液中的F2-异前列腺素。
我们的结果表明,精神分裂症患者中脂质过氧化标志物(TBARS、F2-异前列腺素)水平高于健康受试者,但精神分裂症患者的FRAP低于健康对照组,且在接受测试的抗精神病药物治疗4周后升高。抗精神病药物治疗4周导致阳性和阴性症状量表(PANSS)评估的精神病理症状改善,同时脂质过氧化(F2-异前列腺素、TBARS;p分别为2.9×10、7.6×10)降低,总抗氧化能力(FRAP)增加(p = 5.16×10)。
非典型抗精神病药物,尤其是氯氮平、奥氮平和喹硫平,显示出抗精神病治疗的有效结果,通过减少脂质过氧化和提高血浆总抗氧化活性发挥有益的抗氧化作用。