Abstract
1. 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. 2. 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. 3. 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. 4. 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. 5. In conclusion, our study demonstrates that raxofelast, a new hydrophilic vitamin E-like antioxidant agent, exerts multiple protective effects in carrageenan-induced acute inflammation.
| Original language | English |
|---|---|
| Pages (from-to) | 407-414 |
| Number of pages | 8 |
| Journal | British Journal of Pharmacology |
| Volume | 126 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1999 |
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Keywords
- Carrageenan
- Free radicals
- Inflammation
- Peroxynitrite
- Raxofelast
ASJC Scopus subject areas
- Pharmacology
Cite this
Beneficial effects of raxofelast (IRFI 016), a new hydrophilic vitamin E-like antioxidant, in carrageenan-induced pleurisy. / Cuzzocrea, Salvatore; Costantino, Giuseppina; Mazzon, Emanuela; Caputi, Achille P.
In: British Journal of Pharmacology, Vol. 126, No. 2, 1999, p. 407-414.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Beneficial effects of raxofelast (IRFI 016), a new hydrophilic vitamin E-like antioxidant, in carrageenan-induced pleurisy
AU - Cuzzocrea, Salvatore
AU - Costantino, Giuseppina
AU - Mazzon, Emanuela
AU - Caputi, Achille P.
PY - 1999
Y1 - 1999
N2 - 1. 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. 2. 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. 3. 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. 4. 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. 5. In conclusion, our study demonstrates that raxofelast, a new hydrophilic vitamin E-like antioxidant agent, exerts multiple protective effects in carrageenan-induced acute inflammation.
AB - 1. 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. 2. 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. 3. 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. 4. 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. 5. In conclusion, our study demonstrates that raxofelast, a new hydrophilic vitamin E-like antioxidant agent, exerts multiple protective effects in carrageenan-induced acute inflammation.
KW - Carrageenan
KW - Free radicals
KW - Inflammation
KW - Peroxynitrite
KW - Raxofelast
UR - http://www.scopus.com/inward/record.url?scp=0032907892&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032907892&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0702275
DO - 10.1038/sj.bjp.0702275
M3 - Article
VL - 126
SP - 407
EP - 414
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 2
ER -