7-Hydroxycoumarin modulates the oxidative metabolism, degranulation and microbial killing of human neutrophils

Author(s):Show less -

Kabeya, Luciana M. ^[1] ; Fuzissaki, Carolina N. ^[1] ; Taleb-Contini, Silvia H. ^[1] ; Ferreira, Ana Maria da C. ^[2] ; Naal, Zeki ^[1] ; Santos, Everton O. L. ^[1] ; Figueiredo-Rinhel, Andrea S. G. ^[1] ; Azzolini, Ana Elisa C. S. ^[1] ; Vermelho, Roberta B. ^[1] ; Malvezzi, Alberto ^[2] ; do Amaral, Antonia T. ^[2] ; Lopes, Joao Luis C. ^[1] ; Lucisano-Valim, Yara Maria ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Fis & Quim, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Quim Fundamental, Inst Quim, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Chemico-Biological Interactions; v. 206, n. 1, p. 63-75, OCT 25 2013.
• Web of Science Citations: 7

Abstract

In the present study, we assessed whether 7-hydroxycoumarin (umbelliferone), 7-hydroxy-4-methylcoumarin, and their acetylated analogs modulate some of the effector functions of human neutrophils and display antioxidant activity. These compounds decreased the ability of neutrophils to generate superoxide anion, release primary granule enzymes, and kill Candida albicans. Cytotoxicity did not mediate their inhibitory effect, at least under the assessed conditions. These coumarins scavenged hypochlorous acid and protected ascorbic acid from electrochemical oxidation in cell-free systems. On the other hand, the four coumarins increased the luminol-enhanced chemiluminescence of human neutrophils stimulated with phorbol-12-myristate-13-acetate and serum-opsonized zymosan. Oxidation of the hydroxylated coumarins by the neutrophil myeloperoxidase produced highly reactive coumarin radical intermediates, which mediated the prooxidant effect observed in the luminol-enhanced chemiluminescence assay. These species also oxidized ascorbic acid and the spin traps alpha-(4-pyridy1-1-oxide)-N-tertbutylnitrone and 5-dimethyl-1 -pyrroline-N-oxide. Therefore, 7-hydroxycoumarin and the derivatives investigated here were able to modulate the effector functions of human neutrophils and scavenge reactive oxidizing species; they also generated reactive coumarin derivatives in the presence of myeloperoxidase. Acetylation of the free hydroxyl group, but not addition of the 4-methyl group, suppressed the biological effects of 7-hydroxycoumarin. These findings help clarify how 7-hydroxycoumarin acts on neutrophils to produce relevant anti-inflammatory effects. (C) 2013 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 05/60596-8 - Complex species with potential for application in bio-organics, catalysis, pharmacology and environmental chemistry: conception, preparation, characterization and reactivity
• Grantee: Ana Maria da Costa Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 07/00840-8 - Study of the mechanism of action of coumarin derivatives on the myeloperoxidase activity: investigation about metabolization of these compounds to phenoxyl free radicals, implications on the oxidative stress and modulation of leukocyte functions
• Grantee: Luciana Mariko Kabeya
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 07/02487-3 - Study of the mechanism of action of coumarin derivatives on the myeloperoxidase activity: investigation about metabolization of these compounds to phenoxyl free radicals, implications on the oxidative stress and modulation of leukocyte functions
• Grantee: Yara Maria Lucisano Valim
• Support Opportunities: Regular Research Grants