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

Salvatore Cuzzocrea, Michelle C. McDonald, Helder Mota Filipe, Giuseppina Costantino, Emanuela Mazzon, Sabrina Santagati, Achille P. Caputi, Christoph Thiemermann

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)209-222
Number of pages14
JournalEuropean Journal of Pharmacology
Volume390
Issue number1-2
DOIs
Publication statusPublished - Feb 25 2000

Keywords

  • Carrageenan
  • Inflammation
  • Nitric oxide (NO)
  • Peroxynitrite
  • Superoxide dismutase
  • Tempol

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Fingerprint Dive into the research topics of 'Effects of tempol, a membrane-permeable radical scavenger, in a rodent model of carrageenan-induced pleurisy'. Together they form a unique fingerprint.

  • Cite this

    Cuzzocrea, S., McDonald, M. C., Filipe, H. M., Costantino, G., Mazzon, E., Santagati, S., Caputi, A. P., & Thiemermann, C. (2000). Effects of tempol, a membrane-permeable radical scavenger, in a rodent model of carrageenan-induced pleurisy. European Journal of Pharmacology, 390(1-2), 209-222. https://doi.org/10.1016/S0014-2999(99)00910-3