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The co-catalytic effect of chlorpromazine on peroxidase-mediated oxidation of melatonin: enhanced production of N1-acetyl-N2-formyl-5-methoxykynuramine.
J Pineal Res. 2008 Mar; 44(2):115-20.JP

Abstract

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Ximenes VF
Departamento de Química, Faculdade de Ciências, Universidade Estadual Paulista, Bauru, SP, Brasil. vfximenes@fc.unesp.br
Rodrigues AP
No affiliation info available
Cabello C
No affiliation info available
de Menezes ML
No affiliation info available
Fernandes JR
No affiliation info available

MeSH

AnimalsAntioxidantsAntipsychotic AgentsChlorpromazineHumansKynuramineMelatoninOxidantsOxidation-ReductionPeroxidaseRatsSpectrophotometry, Ultraviolet

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18289161

Citation

Ximenes, Valdecir F., et al. "The Co-catalytic Effect of Chlorpromazine On Peroxidase-mediated Oxidation of Melatonin: Enhanced Production of N1-acetyl-N2-formyl-5-methoxykynuramine." Journal of Pineal Research, vol. 44, no. 2, 2008, pp. 115-20.
Ximenes VF, Rodrigues AP, Cabello C, et al. The co-catalytic effect of chlorpromazine on peroxidase-mediated oxidation of melatonin: enhanced production of N1-acetyl-N2-formyl-5-methoxykynuramine. J Pineal Res. 2008;44(2):115-20.
Ximenes, V. F., Rodrigues, A. P., Cabello, C., de Menezes, M. L., & Fernandes, J. R. (2008). The co-catalytic effect of chlorpromazine on peroxidase-mediated oxidation of melatonin: enhanced production of N1-acetyl-N2-formyl-5-methoxykynuramine. Journal of Pineal Research, 44(2), 115-20. https://doi.org/10.1111/j.1600-079X.2007.00497.x
Ximenes VF, et al. The Co-catalytic Effect of Chlorpromazine On Peroxidase-mediated Oxidation of Melatonin: Enhanced Production of N1-acetyl-N2-formyl-5-methoxykynuramine. J Pineal Res. 2008;44(2):115-20. PubMed PMID: 18289161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The co-catalytic effect of chlorpromazine on peroxidase-mediated oxidation of melatonin: enhanced production of N1-acetyl-N2-formyl-5-methoxykynuramine. AU - Ximenes,Valdecir F, AU - Rodrigues,Ana Paula, AU - Cabello,Cláudio, AU - de Menezes,Manoel L, AU - Fernandes,João Roberto, PY - 2008/2/22/pubmed PY - 2008/5/6/medline PY - 2008/2/22/entrez SP - 115 EP - 20 JF - Journal of pineal research JO - J Pineal Res VL - 44 IS - 2 N2 - 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. SN - 1600-079X UR - https://www.unboundmedicine.com/medline/citation/18289161/The_co_catalytic_effect_of_chlorpromazine_on_peroxidase_mediated_oxidation_of_melatonin:_enhanced_production_of_N1_acetyl_N2_formyl_5_methoxykynuramine_ DB - PRIME DP - Unbound Medicine ER -