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Apocynin inhibits peroxynitrite formation by murine macrophages
Author(s) -
Muijsers R B R,
Van Den Worm E,
Folkerts G,
Beukelman C J,
Koster A S,
Postma D S,
Nijkamp F P
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703401
Subject(s) - apocynin , peroxynitrite , superoxide , chemistry , nitric oxide , nadph oxidase , nitric oxide synthase , peroxynitrous acid , biochemistry , superoxide dismutase , pharmacology , reactive oxygen species , oxidative stress , enzyme , biology , organic chemistry
Peroxynitrite (ONOO − ) the highly reactive coupling product of nitric oxide and superoxide, has been implicated in the pathogenesis of an increasing number of (inflammatory) diseases. At present, however, selective peroxynitrite antagonizing agents with therapeutic potential are not available. Therefore, the NADPH‐oxidase inhibitor apocynin (4‐hydroxy‐3‐methoxy‐acetophenone) was tested for its ability to inhibit peroxynitrite formation in vitroThe murine macrophage cell‐line J774A.1, stimulated with IFNγ/LPS, was used as a model. Conversion of 123‐dihydrorhodamine (123‐DHR) to its oxidation product 123‐rhodamine was used to measure peroxynitrite production. Stimulated peroxynitrite formation could be completely inhibited by apocynin, by the superoxide scavenger TEMPO as well as by the nitric oxide synthase inhibitor aminoguanidine. Apocynin and aminoguanidine specifically inhibited superoxide and nitric oxide formation respectively as confirmed by measuring lucigenin enhanced chemiluminescence and nitrite accumulation. It is concluded that J774A.1 macrophages produce significant amounts of peroxynitrite, which is associated with nitric oxide production and NADPH‐oxidase dependent superoxide formation. The NADPH‐oxidase inhibitor apocynin proved to be a potent inhibitor of both superoxide and peroxynitrite formation by macrophages, which may be of future therapeutic significance in a wide range of inflammatory disorders.British Journal of Pharmacology (2000) 130 , 932–936; doi: 10.1038/sj.bjp.0703401