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Another characteristic of the esters, and different from apo-
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that the catechol moiety is easily oxidized compared to the methoxy
catechol apocynin; hence, a lower dependency of the catalytic af-
fect of MPO could be expected.
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The biological effect of the esters on NADPH oxidase in PMNs
had consequences on the production of HOCl by these cells. This
finding is highly significant because of the deleterious effect of
HOCl on biomolecules and its correlation with tissue injury in sev-
eral pathologies, including cardiovascular diseases, is widely ac-
cepted [41, 42]. Our findings clearly showed that the inhibition of
release of HOCl is not related to the scavenger effects on HOCl or
inhibition of the enzymatic chlorinating activity of MPO. Hence,
the logical conclusion is the inhibition of production of O2•-, which
is the precursor of H2O2, and through MPO, of HOCl.
[12]
[13]
[14]
[15]
[16]
[17]
CONCLUSION
Considering the well-established relationship between several
inflammatory and degenerative diseases and the activation of
NADPH oxidase as a primary non-mitochondrial source of O2•-, the
development of drugs able to inhibit this enzymatic source of ROS
could bring enormous benefits for the treatment of these diseases. A
common characteristic of NADPH oxidase inhibitors such as
flavanols [43], catechols [44], methoxy-substituted catechols [45],
diphenylene iodonium [46], etc, is the presence of a redox active or
electrophilic moiety; however, here we demonstrated for the first
time that the hydrophobicity is also relevant. This dependence is an
indication that the membrane permeability and/or accessibility to
the NADPH oxidase complex, which is a multi-component mem-
brane complex, can be an important factor for the development of a
NADPH oxidase inhibitor.
[18]
[19]
[20]
[21]
CONFLICT OF INTEREST
[22]
[23]
[24]
The author(s) confirm that this article content has no conflicts
of interest.
ACKNOWLEDGEMENTS
This work was supported by grants from Fundação de Amparo
à Pesquisa do Estado de São Paulo (Fapesp) and from Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
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