No beneficial effect of n-acelylcysteine treatment on broncho-alveolar lavage fluid variables in acute nitrogen dioxide intoxicated rats

In previous studies a rat inhalation model was developed to investigate the efficacy of treatment in acute NO₂ intoxication. N-acetylcysteine (NAC) was administered intravenously to study its effect on biochemical variables in broncho-alveolar lavage fluid in acute NO₂ intoxicated rats. It was decided to start the intravenous administration of NAC 24 h before the exposure to NO₂ to induce higher intracellular glutathione (GSH) levels in lung cells of NAC-treated rats compared to not NAC-treated rats. Because, on theoretical grounds, the therapeutic effect of NAC may be expected to be especially marked during the first 24 h after exposure, the rats were observed for a period of 24 h and were then killed for investigation. A loading dose of 85 mg kg^-1 h^-1 or 170 mg kg^-1 h^-1 was followed by a continuous infusion (until autopsy) with a dose of 225 mg kg^-1 24 h^-1 or 450 mg kg^-1 24 h^-1 respectively. Twenty four hours after exposure to 175 ppm NO₂ (1 ppm is 1.88 mg m^-3) for 10 min, NAC did not reduce the increase of variables in broncho-alveolar lavage fluid which reflect the severity of lung damage. The protein and albumin concentration and the activities of anglotensin converting enzyme and alkaline phosphatase in broncho-alveolar lavage fluid after NO₂ exposure were even more increased in the NAC-treated than in the saline-treated rats, but none of the differences was statistically significant. In sham exposed rats no effect of NAC was observed.