Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid

Abstract

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 phosphatebuffered 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 IC 50 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.

Antioxidant and antifungal activities of Camellia sinensis (L.) Kuntze leaves obtained by different forms of production

“…The remaining HOCl was detected by TMB 0.014 mol/L, which has a maximum oxidation at 652 nm. The decrease in TMB absorbance represents the antioxidant activity of each tea (Ximenes et al, 2005).…”

Protective action of indole‐3‐acetic acid on induced hepatocarcinoma in mice

“…Animals can obtain IAA from intestinal absorption of a diet rich in vegetables or from synthesis from tryptophan in various tissues. 6 Studies have showed that IAA can provide antioxidant activity by inhibiting lipid peroxidation similarly to other indolic compounds 7,8 and provide semen preservation at similar concentrations 9 in water coconut 10 ; in addition, IAA have a topic antiinflammatory action. 11 Recent studies have shown that oral or subcutaneous administration of IAA can promote a possible beneficial effect by increasing the phagocytic capacity of rat neutrophils.…”

Effect of indole‐3‐acetic acid administration by gavage and by subcutaneous injection on rat leukocytes

“…[16][17][18] One other study showed that IAA selectively inhibits the excessive production of hypochlorous acid by activated leukocytes, a compound that has been implicated in tissue damage from chronic inflammatory diseases. 19 Recent studies have shown that subcutaneous IAA promotes an increase in phagocytic capacity, is accompanied by alteration in hydrogen peroxide production in neutrophils, but does not show a pro-oxidant effect in leukocytes 20 or liver. 21 The information above led us to study the effect of IAA administered subcutaneously and by gavage to rats at low doses (equal to or less than 40 mg of IAA per kg of body mass) on neutrophil functions and cell death of neutrophils and lymphocytes.…”