NO BENEFICIAL EFFECT OF N-ACETYLCYSTEINE TREATMENT ON BRONCHOALVEOLARLAVAGE FLUID VARIABLES IN ACUTE NITROGEN-DIOXIDE INTOXICATED RATS

1 In previous studies a rat inhalation model was developed to investig ate the efficacy of treatment in acute NO2 intoxication, 2 N-acetylcys teine (NAC) was administered intravenously to study its effect on bioc hemical variables in broncho-alveolar lavage fluid in acute NO2 intoxi cated rats. It was decided to start the intravenous administration of NAC 24 h before the exposure to NO2 to induce higher intracellular glu tathione (GSH) levels in lung cells of NAC-treated rats compared to no t NAC-treated rats. Because, on theoretical grounds, the therapeutic e ffect 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 w ere 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, 3 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 v ariables in bronchoalveolar lavage fluid which reflect the severity of lung damage. 4 The protein and albumin concentration and the activiti es of angiotensin converting enzyme and alkaline phosphatase in bronch o-alveolar lavage fluid after NO2 exposure were even more increased in the NAC-treated than in the saline-treated rats, but none of the diff erences was statistically significant. 5 In sham exposed rats no effec t of NAC was observed.