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

Oxidative stress has been suggested as a potential mechanism in the pathoge nesis 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 characte rized by fluid accumulation in the pleural cavity that contained many neutr ophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor alpha, and interleukin 1 beta. All parameters of inflammation were a ttenuated by NAC treatment. Furthermore, carrageenan induced an up-regulati on of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosin e and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochem ical analysis of lung tissues. The degree of staining for the ICAM-1, P-sel ectin, nitrotyrosine, and PARS was reduced by NAG. In vivo NAC treatment si gnificantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA dama ge, an decrease in mitochondrial respiration, and partially restored the ce llular level of NAD+ in ex vivo macrophages harvested from the pleural cavi ty of rats subjected to carrageenan-induced pleurisy. A significant alterat ion in the morphology of red blood cells was observed 24 h after carrageena n administration. NAC treatment has the ability to significantly diminish t he red blood cell alteration. Our results clearly demonstrate that NAC trea tment exerts a protective effect and clearly indicate that NAC offers a nov el therapeutic approach for the management of lung injury where radicals ha ve been postulated to play a role.