Data/hora: 04/06/2024 02:27:39

Provedor de dados: | 56
País: | Brazil
Título: | Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid
Autores: | Ximenes,V.F.; Paino,I.M.M.; Faria-Oliveira,O.M.M. de; Fonseca,L.M. da; Brunetti,I.L.
Data: | 2005-11-01
Ano: | 2005
Palavras-chave: | Leukocytes; Myeloperoxidase; Hypochlorous acid; Indole ring; Melatonin; Indole-3-acetic acid.
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.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005001100003
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X2005001100003
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.38 n.11 2005
Fonte: | info:eu-repo/semantics/openAccess