Effects of tempol, a membrane-permeable radical scavenger, in a rodent model of carrageenan-induced pleurisy

Carrageenan causes enhanced formation of reactive oxygen species, which con tribute to the pathophysiology of inflammation. We have investigated the ef fects 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 depend ently. Tempol also attenuated the lung injury (histology) as well as the in crease in the tissue levels of myeloperoxidase and malondialdehyde caused b y 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-trea ted rats. Lung tissue sections from carrageenan-treated rats also showed po sitive staining for poly-(ADP-ribose) synthetase (PARS). The degree of stai ning for nitrotyrosine and PARS was markedly reduced in tissue sections obt ained from carrageenan-treated rats, which had received tempol (100 mg/kg). Furthermore, treatment of rats with tempol significantly reduced (i) the f ormation of peroxynitrite, (ii) the DNA damage, (iii) the impairment in mit ochondrial respiration, and (iv) the fall in the cellular level of NAD(+) o bserved in macrophages harvested from the pleural cavity of rats treated wi th carrageenan. Tempol also attenuated the cell injury caused by hydrogen p eroxide (1 mM) in cultured human endothelial cells. This study provides the first evidence that tempol, a small molecule which permeates biological me mbranes and scavenges ROS, attenuates the degree of inflammation and tissue damage associated with carageenan-induced pleurisy in the rat. The mechani sms of the anti-inflammatory effect of tempol are discussed. (C) 2000 Elsev ier Science B.V. All rights reserved.