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Oxidative Medicine and Cellular Longevity
Volume 2013 (2013), Article ID 136570, 10 pages
http://dx.doi.org/10.1155/2013/136570
Research Article

Study of Possible Mechanisms Involved in the Inhibitory Effects of Coumarin Derivatives on Neutrophil Activity

1Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovakia
2Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v. v. i., Flemingovo náměsti 2, 161 10 Prague, Czech Republic
3Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech Republic

Received 22 July 2013; Revised 17 October 2013; Accepted 17 October 2013

Academic Editor: David Vauzour

Copyright © 2013 Katarína Drábiková et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

To specify the site of action of the synthetic coumarin derivatives 7-hydroxy-3-(4′-hydroxyphenyl) coumarin (HHC) and 7-hydroxy-3-(4′-hydroxyphenyl) dihydrocoumarin (HHDC), we evaluated their effects on extra- and intracellular reactive oxygen species (ROS) formation in phorbol-myristate-13-acetate (PMA) stimulated human neutrophils. We studied also the effects of HHC and HHDC on possible molecular mechanisms which participate in the activation of NADPH oxidase, that is, on PKC activity, on phosphorylation of some PKC isoforms (α, βII, and δ), and on phosphorylation of the NADPH oxidase subunit p40phox. Without affecting cytotoxicity, both coumarines tested were effective inhibitors/scavengers of ROS produced by neutrophils on extracellular level. HHC markedly diminished oxidant production and also, intracellularly, decreased PKC activity and partly phosphorylation of PKCα, βII. On the other hand, we did not observe any effect of coumarin derivatives on phosphorylation of PKCδ and on phosphorylation of the NADPH oxidase subunit p40phox, which were suggested to be involved in the PMA-dependent intracellular activation process. In agreement with our previous findings, we assume that the different molecular structures of HHC and HHDC with their different physicochemical and free radical scavenging characteristics are responsible for their diverse effects on the parameters tested.