TY - JOUR
T1 - Effects of tempol, a membrane-permeable radical scavenger, in a rodent model of carrageenan-induced pleurisy
AU - Cuzzocrea, Salvatore
AU - McDonald, Michelle C.
AU - Filipe, Helder Mota
AU - Costantino, Giuseppina
AU - Mazzon, Emanuela
AU - Santagati, Sabrina
AU - Caputi, Achille P.
AU - Thiemermann, Christoph
PY - 2000/2/25
Y1 - 2000/2/25
N2 - Carrageenan causes enhanced formation of reactive oxygen species, which contribute to the pathophysiology of inflammation. We have investigated the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to carrageenan-induced pleurisy. Treatment of rats with tempol (10, 30, or 100 mg/kg 15 min prior to carrageenan) attenuated the pleural exudation and the migration of polymorphonuclear cells caused by carrageenan dose dependently. Tempol also attenuated the lung injury (histology) as well as the increase in the tissue levels of myeloperoxidase and malondialdehyde caused by carrageenan in the lung. However, tempol did not inhibit the activity of inducible nitric oxide synthase in the lungs. Immunohistochemical analysis for nitrotyrosine revealed positive staining in lungs from carrageenan-treated rats. Lung tissue sections from carrageenan-treated rats also showed positive staining for poly-(ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and PARS was markedly reduced in tissue sections obtained from carrageenan-treated rats, which had received tempol (100 mg/kg). Furthermore, treatment of rats with tempol significantly reduced (i) the formation of peroxynitrite, (ii) the DNA damage, (iii) the impairment in mitochondrial respiration, and (iv) the fall in the cellular level of NAD+ observed in macrophages harvested from the pleural cavity of rats treated with carrageenan. Tempol also attenuated the cell injury caused by hydrogen peroxide (1 mM) in cultured human endothelial cells. This study provides the first evidence that tempol, a small molecule which permeates biological membranes and scavenges ROS, attenuates the degree of inflammation and tissue damage associated with carageenan-induced pleurisy in the rat. The mechanisms of the anti-inflammatory effect of tempol are discussed. Copyright (C) 2000 Elsevier Science B.V.
AB - Carrageenan causes enhanced formation of reactive oxygen species, which contribute to the pathophysiology of inflammation. We have investigated the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to carrageenan-induced pleurisy. Treatment of rats with tempol (10, 30, or 100 mg/kg 15 min prior to carrageenan) attenuated the pleural exudation and the migration of polymorphonuclear cells caused by carrageenan dose dependently. Tempol also attenuated the lung injury (histology) as well as the increase in the tissue levels of myeloperoxidase and malondialdehyde caused by carrageenan in the lung. However, tempol did not inhibit the activity of inducible nitric oxide synthase in the lungs. Immunohistochemical analysis for nitrotyrosine revealed positive staining in lungs from carrageenan-treated rats. Lung tissue sections from carrageenan-treated rats also showed positive staining for poly-(ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and PARS was markedly reduced in tissue sections obtained from carrageenan-treated rats, which had received tempol (100 mg/kg). Furthermore, treatment of rats with tempol significantly reduced (i) the formation of peroxynitrite, (ii) the DNA damage, (iii) the impairment in mitochondrial respiration, and (iv) the fall in the cellular level of NAD+ observed in macrophages harvested from the pleural cavity of rats treated with carrageenan. Tempol also attenuated the cell injury caused by hydrogen peroxide (1 mM) in cultured human endothelial cells. This study provides the first evidence that tempol, a small molecule which permeates biological membranes and scavenges ROS, attenuates the degree of inflammation and tissue damage associated with carageenan-induced pleurisy in the rat. The mechanisms of the anti-inflammatory effect of tempol are discussed. Copyright (C) 2000 Elsevier Science B.V.
KW - Carrageenan
KW - Inflammation
KW - Nitric oxide (NO)
KW - Peroxynitrite
KW - Superoxide dismutase
KW - Tempol
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U2 - 10.1016/S0014-2999(99)00910-3
DO - 10.1016/S0014-2999(99)00910-3
M3 - Article
C2 - 10708726
AN - SCOPUS:0034712003
VL - 390
SP - 209
EP - 222
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-2
ER -