The co-catalytic effect of chlorpromazine on peroxidase-mediated oxidation of melatonin: enhanced production of N1-acetyl-N2-formyl-5-methoxykynuramine
| Autor: | Manoel Lima de Menezes, João Roberto Fernandes, Ana Paula Rodrigues, Cláudio Cabello, Valdecir Farias Ximenes |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Antioxidant
Chlorpromazine Kynuramine medicine.medical_treatment Pharmacology Horseradish peroxidase Antioxidants Melatonin Endocrinology medicine Animals Humans Peroxidase chemistry.chemical_classification biology Chemistry Antagonist Oxidants Rats Enzyme Biochemistry Myeloperoxidase biology.protein Spectrophotometry Ultraviolet Oxidation-Reduction hormones hormone substitutes and hormone antagonists Antipsychotic Agents medicine.drug |
| Zdroj: | Journal of Pineal Research. 44:115-120 |
| ISSN: | 1600-079X 0742-3098 |
| Popis: | Accumulating evidence points to relationships between increased production of reactive oxygen or decreased antioxidant protection in schizophrenic patients. Chlorpromazine (CPZ), which remains a benchmark treatment for people with schizophrenia, has been described as a pro-oxidant compound. Because the antioxidant compound melatonin exerts protective effects against CPZ-induced liver disease in rats, in this investigation, our main objective was to study the effect of CPZ as a co-catalyst of peroxidase-mediated oxidation of melatonin. We found that melatonin was an excellent reductor agent of preformed CPZ cation radical (CPZ(*+)). The addition of CPZ during the horseradish peroxidase (HRP)-catalyzed oxidation of melatonin provoked a significant increase in the rate of oxidation and production of N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK). Similar results were obtained using myeloperoxidase. The effect of CPZ on melatonin oxidation was rather higher at alkaline pH. At pH 9.0, the efficiency of oxidation of melatonin was 15 times higher and the production of AFMK was 30 times higher as compared with the assays in the absence of CPZ. We suggest that CPZ is able to exacerbate the rate of oxidation of melatonin by an electron transfer mechanism where CPZ(*+), generated during the peroxidase-catalyzed oxidation, is able to efficiently oxidize melatonin. |
| Databáze: | OpenAIRE |
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