Activation of chlorpromazine by the myeloperoxidase system of the human neutrophil

Simple item page
dc.contributor.authorVan Zyl J.M.
dc.contributor.authorBasson K.
dc.contributor.authorKriegler A.
dc.contributor.authorVan Der Walt B.J.
dc.date.accessioned2011-05-15T16:01:18Z
dc.date.available2011-05-15T16:01:18Z
dc.date.issued1990
dc.description.abstractThe univalent oxidation of chlorpromazine (CPZ) by the myeloperoxidase (MPO-H2O2 system led to the formation of a cation free radical (CPZ+.) which was observed optically at 527 nm. CPZ protected MPO against loss of catalytic activity when co-oxidized in a MPO-Cl--H2O2 system. Due to the stability of CPZ+. either further oxidation, or reduction back to the mother compound, become important mechanisms for disappearance of the free radical. Thus, the rate of formation and decay of CPZ+. were higher in the presence of Cl- than in its absence, since the radical can also be oxidized further by hypochlorous acid (HOCl), which is formed in the MPO-Cl--H2O2 system. Decay of CPZ+. can also be due to electron acceptance from ascorbic acid or oxygenated haemoglobin (HbO2), resulting in regeneration of CPZ. When CPZ+. was generated in the MPO-H2O2 system, addition of HbO2 resulted in a sudden decrease in CPZ+. absorbance at 527 nm and a concomitant formation of metHb. When HbO2 was not added, the decay of CPZ+. was much slower. CPZ (in the absence of the MPO system) also stimulated the oxidation of HbO2 in the presence of 20 μM H2O2, but this reaction was considerably slower than when CPZ+. (generated by the MPO system) was allowed to react directly with HbO2. These results suggest that HbO2 was oxidized by CPZ+. To study the effect of CPZ intermediates, thyroglobulin (TG) was used as a model polypeptide. Chlorinated oxidants formed in the MPO system (in the absence of CPZ) induced TG peptide bond splitting. In contrast, CPZ metabolites generated by the MPO system (in the absence of Cl-) induced polymerization of TG, as revealed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE).
dc.description.versionArticle
dc.identifier.citationBiochemical Pharmacology
dc.identifier.citation40
dc.identifier.citation5
dc.identifier.issn62952
dc.identifier.other10.1016/0006-2952(90)90478-4
dc.identifier.urihttp://hdl.handle.net/10019.1/11909
dc.subjectchlorpromazine
dc.subjectfree radical
dc.subjectmethemoglobin
dc.subjectmyeloperoxidase
dc.subjectoxyhemoglobin
dc.subjectthyroglobulin
dc.subjectantioxidant activity
dc.subjectarticle
dc.subjectenzyme activity
dc.subjecthuman
dc.subjecthuman cell
dc.subjectmetabolic activation
dc.subjectneutrophil
dc.subjectpolyacrylamide gel electrophoresis
dc.subjectpriority journal
dc.subjectspectrophotometry
dc.subjectChlorpromazine
dc.subjectElectrophoresis, Polyacrylamide Gel
dc.subjectEnzyme Activation
dc.subjectFree Radicals
dc.subjectHuman
dc.subjectMethemoglobin
dc.subjectNeutrophils
dc.subjectPeroxidase
dc.subjectSupport, Non-U.S. Gov't
dc.subjectThyroglobulin
dc.titleActivation of chlorpromazine by the myeloperoxidase system of the human neutrophil
dc.typeArticle
Files
Collections
Stellenbosch University - Scopus Publications