title: Paliperidone regulates intracellular redox system in rat brain: Role of purine mechanism.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Kadir
authors.initials: K
authors.lastname: Demirci
authors.forename: Ramazan
authors.initials: R
authors.lastname: Özçankaya
authors.forename: H Ramazan
authors.initials: HR
authors.lastname: Yilmaz
authors.forename: Ayşe
authors.initials: A
authors.lastname: Yiğit
authors.forename: Abdülhadi Cihangir
authors.initials: AC
authors.lastname: Uğuz
authors.forename: Kadir
authors.initials: K
authors.lastname: Karakuş
authors.forename: Arif
authors.initials: A
authors.lastname: Demirdaş
authors.forename: Abdullah
authors.initials: A
authors.lastname: Akpınar
mesh_terms: D000243:Adenosine Deaminase / Q000032:analysis; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002374:Catalase / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009569:Nitric Oxide / Q000032:analysis; D010084:Oxidation-Reduction; D000068882:Paliperidone Palmitate / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000032:analysis; D014969:Xanthine Oxidase / Q000032:analysis
chemical_list: D014150:Antipsychotic Agents; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011687:Purines; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; C548484:Ada protein, rat; D000243:Adenosine Deaminase; D000068882:Paliperidone Palmitate
keywords: Adenosine deaminase; Catalase; Glutathione peroxidase; Malondialdehyde; Nitric oxide; Paliperidone; Superoxide dismutase; Xanthine oxidase