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Beneficial effects of raxofelast (IRFI 016), a new hydrophilic vitamin E‐like antioxidant, in carrageenan‐induced pleurisy
Author(s) -
Cuzzocrea Salvatore,
Costantino Giuseppina,
Mazzon Emanuela,
Caputi Achille P
Publication year - 1999
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.0702275
Subject(s) - carrageenan , peroxynitrite , nitrotyrosine , pleurisy , chemistry , pharmacology , in vivo , antioxidant , myeloperoxidase , malondialdehyde , inflammation , vitamin e , lipid peroxidation , biochemistry , superoxide dismutase , superoxide , medicine , immunology , nitric oxide synthase , pleural effusion , biology , enzyme , microbiology and biotechnology
Peroxynitrite is a strong oxidant that results from reaction between NO and superoxide. It has been recently proposed that peroxynitrite plays a pathogenetic role in inflammatory processes. Here we have investigated the therapeutic efficacy of raxofelast, a new hydrophilic vitamin E‐like antioxidant agent, in rats subjected to carrageenan‐induced pleurisy.In vivo treatment with raxofelast (5, 10, 20 mg kg −1 intraperitoneally 5 min before carrageenan) prevented in a dose dependent manner carrageenan‐induced pleural exudation and polymorphonuclear migration in rats subjected to carrageenan‐induced pleurisy. Lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels, as well as histological organ injury were significantly reduced by raxofelast. Immunohistochemical analysis for nitrotyrosine, a footprint of peroxynitrite, revealed a positive staining in lungs from carrageenan‐treated rats. No positive nitrotyrosine staining was found in the lungs of the carrageenan‐treated rats, which received raxofelast (20 mg kg −1 ) treatment. Furthermore, in vivo raxofelast (5, 10, 20 mg kg −1 ) treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine 123, prevented the appearance of DNA damage, the decrease in mitochondrial respiration and partially restored the cellular level of NAD + in ex vivo macrophages harvested from the pleural cavity of rats subjected to carrageenan‐induced pleurisy. In conclusion, our study demonstrates that raxofelast, a new hydrophilic vitamin E‐like antioxidant agent, exerts multiple protective effects in carrageenan‐induced acute inflammation.British Journal of Pharmacology (1999) 126 , 407–414; doi: 10.1038/sj.bjp.0702275