Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat

Salvatore Cuzzocrea, Emanuela Mazzon, Laura Dugo, Ivana Serraino, Antonio Ciccolo, Tommaso Centorrino, Angela De Sarro, Achille P. Caputi

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a free radical scavenger, was evaluated in an experimental model of lung injury (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor α, and interleukin 1 β. All parameters of inflammation were attenuated by NAC treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA damage, an 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. A significant alteration in the morphology of red blood cells was observed 24 h after carrageenan administration. NAC treatment has the ability to significantly diminish the red blood cell alteration. Our results clearly demonstrate that NAC treatment exerts a protective effect and clearly indicate that NAC offers a novel therapeutic approach for the management of lung injury where radicals have been postulated to play a role. - Cuzzocrea, S., Mazzon, E., Dugo, L., Serraino, I., Ciccolo, A., Centorrino, T., De Sarro, A., Caputi, A. P. Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat.

Original languageEnglish
Pages (from-to)1187-1200
Number of pages14
JournalFASEB Journal
Volume15
Issue number7
DOIs
Publication statusPublished - 2001

Fingerprint

acetylcysteine
Carrageenan
carrageenan
Acetylcysteine
Lung Injury
protective effect
Rats
Blood
erythrocytes
Erythrocytes
lungs
Cells
rats
Pleural Cavity
Poly Adenosine Diphosphate Ribose
NAD ADP-ribosyltransferase
Pleurisy
P-Selectin
inflammation
Intercellular Adhesion Molecule-1

Keywords

  • Inflammation
  • N-acetylcysteine
  • Nitric oxide
  • Peroxynitrite
  • Superoxide

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat. / Cuzzocrea, Salvatore; Mazzon, Emanuela; Dugo, Laura; Serraino, Ivana; Ciccolo, Antonio; Centorrino, Tommaso; De Sarro, Angela; Caputi, Achille P.

In: FASEB Journal, Vol. 15, No. 7, 2001, p. 1187-1200.

Research output: Contribution to journalArticle

Cuzzocrea, S, Mazzon, E, Dugo, L, Serraino, I, Ciccolo, A, Centorrino, T, De Sarro, A & Caputi, AP 2001, 'Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat', FASEB Journal, vol. 15, no. 7, pp. 1187-1200. https://doi.org/10.1096/fj.00-0526hyp
Cuzzocrea, Salvatore ; Mazzon, Emanuela ; Dugo, Laura ; Serraino, Ivana ; Ciccolo, Antonio ; Centorrino, Tommaso ; De Sarro, Angela ; Caputi, Achille P. / Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat. In: FASEB Journal. 2001 ; Vol. 15, No. 7. pp. 1187-1200.
@article{4a486dc7c3ec4de5a7508bbe7a33be63,
title = "Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat",
abstract = "Oxidative stress has been suggested as a potential mechanism in the pathogenesis of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a free radical scavenger, was evaluated in an experimental model of lung injury (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor α, and interleukin 1 β. All parameters of inflammation were attenuated by NAC treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA damage, an 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. A significant alteration in the morphology of red blood cells was observed 24 h after carrageenan administration. NAC treatment has the ability to significantly diminish the red blood cell alteration. Our results clearly demonstrate that NAC treatment exerts a protective effect and clearly indicate that NAC offers a novel therapeutic approach for the management of lung injury where radicals have been postulated to play a role. - Cuzzocrea, S., Mazzon, E., Dugo, L., Serraino, I., Ciccolo, A., Centorrino, T., De Sarro, A., Caputi, A. P. Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat.",
keywords = "Inflammation, N-acetylcysteine, Nitric oxide, Peroxynitrite, Superoxide",
author = "Salvatore Cuzzocrea and Emanuela Mazzon and Laura Dugo and Ivana Serraino and Antonio Ciccolo and Tommaso Centorrino and {De Sarro}, Angela and Caputi, {Achille P.}",
year = "2001",
doi = "10.1096/fj.00-0526hyp",
language = "English",
volume = "15",
pages = "1187--1200",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "7",

}

TY - JOUR

T1 - Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat

AU - Cuzzocrea, Salvatore

AU - Mazzon, Emanuela

AU - Dugo, Laura

AU - Serraino, Ivana

AU - Ciccolo, Antonio

AU - Centorrino, Tommaso

AU - De Sarro, Angela

AU - Caputi, Achille P.

PY - 2001

Y1 - 2001

N2 - Oxidative stress has been suggested as a potential mechanism in the pathogenesis of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a free radical scavenger, was evaluated in an experimental model of lung injury (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor α, and interleukin 1 β. All parameters of inflammation were attenuated by NAC treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA damage, an 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. A significant alteration in the morphology of red blood cells was observed 24 h after carrageenan administration. NAC treatment has the ability to significantly diminish the red blood cell alteration. Our results clearly demonstrate that NAC treatment exerts a protective effect and clearly indicate that NAC offers a novel therapeutic approach for the management of lung injury where radicals have been postulated to play a role. - Cuzzocrea, S., Mazzon, E., Dugo, L., Serraino, I., Ciccolo, A., Centorrino, T., De Sarro, A., Caputi, A. P. Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat.

AB - Oxidative stress has been suggested as a potential mechanism in the pathogenesis of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a free radical scavenger, was evaluated in an experimental model of lung injury (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor α, and interleukin 1 β. All parameters of inflammation were attenuated by NAC treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA damage, an 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. A significant alteration in the morphology of red blood cells was observed 24 h after carrageenan administration. NAC treatment has the ability to significantly diminish the red blood cell alteration. Our results clearly demonstrate that NAC treatment exerts a protective effect and clearly indicate that NAC offers a novel therapeutic approach for the management of lung injury where radicals have been postulated to play a role. - Cuzzocrea, S., Mazzon, E., Dugo, L., Serraino, I., Ciccolo, A., Centorrino, T., De Sarro, A., Caputi, A. P. Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat.

KW - Inflammation

KW - N-acetylcysteine

KW - Nitric oxide

KW - Peroxynitrite

KW - Superoxide

UR - http://www.scopus.com/inward/record.url?scp=0035025056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035025056&partnerID=8YFLogxK

U2 - 10.1096/fj.00-0526hyp

DO - 10.1096/fj.00-0526hyp

M3 - Article

VL - 15

SP - 1187

EP - 1200

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 7

ER -