Demirci Kadir, Özçankaya Ramazan, Yilmaz H Ramazan, Yiğit Ayşe, Uğuz Abdülhadi Cihangir, Karakuş Kadir, Demirdaş Arif, Akpınar Abdullah
Redox Rep. 2015 Jul;20(4):170-6. doi: 10.1179/1351000214Y.0000000122. Epub 2014 Dec 29.
The treatment of schizophrenia is multifactorial, with antipsychotic medications comprising a major part of treatment. Paliperidone is a newly commercialized antipsychotic whose formulation includes the principal active metabolite risperidone, 9-hydroxyrisperidone. Ever since the relationship between schizophrenia and oxidative stress was first demonstrated, many studies have been conducted in order to probe the potential protective effects of antipsychotic drugs on the oxidant-antioxidant system and lipid peroxidation. The basic aim of this study is to determine the effects of the newly marketed drug paliperidone on the activities of the enzymes adenosine deaminase (ADA), xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as on malondialdehyde (MDA) and nitric oxide (NO) levels in rat brain tissues.
Twenty male Sprague-Dawley rats were used for the study, which were divided into two equal groups. The first was the control group (n = 10) and the second was the paliperidone group (n = 10). Saline was administered once daily for 14 days in the control group. In the paliperidone group, paliperidone was administered once daily with a dose of 1 mg/kg for 14 days. All rats were sacrificed at the end of the fourteenth day. Brain samples were collected and then analyzed.
Our results demonstrated that paliperidone significantly decreased the activities of ADA (P = 0.015), XO (P = 0.0001), and CAT (P = 0.004) while insignificantly increasing the activity of SOD (P = 0.49), MDA (P = 0.71), and NO (P = 0.26) levels in rat brain tissues. In addition, paliperidone insignificantly decreased the activity of GSH-Px (P = 0.30) compared to the control group in rat brain tissues.
In conclusion, the data obtained in this study suggest that paliperidone can positively alter antioxidant status and, accordingly, can offer positive outcomes in the treatment of schizophrenia by reducing activity in the enzymes ADA and XO, which are associated with purine metabolism. We believe that such a comprehensive approach used with other antipsychotic drugs warrants further study.
精神分裂症的治疗是多方面的，抗精神病药物是治疗的主要组成部分。帕利哌酮是一种新上市的抗精神病药物，其制剂包含主要活性代谢物利培酮，即9-羟基利培酮。自从首次证明精神分裂症与氧化应激之间的关系以来，已经进行了许多研究，以探究抗精神病药物对氧化-抗氧化系统和脂质过氧化的潜在保护作用。本研究的基本目的是确定新上市的药物帕利哌酮对大鼠脑组织中腺苷脱氨酶（ADA）、黄嘌呤氧化酶（XO）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性以及丙二醛（MDA）和一氧化氮（NO）水平的影响。
本研究使用20只雄性Sprague-Dawley大鼠，将其分为两组，每组10只。第一组为对照组，第二组为帕利哌酮组。对照组每天给予一次生理盐水，持续14天。在帕利哌酮组中，每天给予一次剂量为1mg/kg的帕利哌酮，持续14天。在第十四天结束时处死所有大鼠。收集脑样本并进行分析。
我们的结果表明，帕利哌酮显著降低了大鼠脑组织中ADA（P = 0.015）、XO（P = 0.0001）和CAT（P = 0.004）的活性，同时对SOD（P = 0.49）、MDA（P = 0.71）和NO（P = 0.26）水平的升高不显著。此外，与对照组相比，帕利哌酮对大鼠脑组织中GSH-Px活性的降低不显著（P = 0.30）。
总之，本研究获得的数据表明，帕利哌酮可以积极改变抗氧化状态，因此，通过降低与嘌呤代谢相关的ADA和XO酶的活性，可以在精神分裂症治疗中提供积极的结果。我们认为，将这种综合方法与其他抗精神病药物一起使用值得进一步研究。
