No beneficial effect of N-acetylcysteine treatment on broncho-alveolar lavage fluid variables in acute nitrogen dioxide intoxicated rats.
1. In previous studies a rat inhalation model was developed to investigate the efficacy of treatment in acute NO2 intoxication. 2. 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. 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 variables in broncho-alveolar lavage fluid which reflect the severity of lung damage. 4. The protein and albumin concentration and the activities of angiotensin 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. 5. In sham exposed rats no effect of NAC was observed.
Meulenbelt
J
J
National Poison Control Centre, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
van Bree
L
L
Dormans
J A
JA
Sangster
B
B
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D005260:Female; D009569:Nitric Oxide / Q000506:poisoning*; D011041:Poisoning / Q000188:drug therapy; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D000111:Acetylcysteine