Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid
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Data
2005-11-01
Autores
Ximenes, V.F. [UNESP]
Paino, I.M.M. [UNESP]
Faria-Oliveira, O.M.M. de [UNESP]
Fonseca, L.M. da [UNESP]
Brunetti, Iguatemy Lourenço [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Associação Brasileira de Divulgação Científica (ABRADIC)
Resumo
Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37ºC in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 µM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 ± 0.03 and 5.0 ± 1.0 µM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.
Descrição
Palavras-chave
Leukocytes, Myeloperoxidase, Hypochlorous acid, Indole ring, Melatonin, Indole-3-acetic acid
Como citar
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 38, n. 11, p. 1575-1583, 2005.