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No Beneficial Effect of N-acetylcysteine Treatment on Broncho-alveolar Lavage Fluid Variables in Acute Nitrogen Dioxide Intoxicated Rats

National Poison Control Centre, PO Box 1, 3720 BA Bilthoven, NL, Department of Intensive Care and Clinical Toxicology, University Hospital Utrecht, Utrecht, The Netherlands

L. van Bree

Laboratory for Toxicology, PO Box 1, 3720 BA Bilthoven, NL

J.A.M.A. Dormans

Laboratory for Pathology of the National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands

B. Sangster

Department of Intensive Care and Clinical Toxicology, University Hospital Utrecht, Utrecht, The Netherlands

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 bronchoalveolar 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 NO ₂ 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.

Human & Experimental Toxicology, Vol. 13, No. 7, 472-477 (1994)
DOI: 10.1177/096032719401300704


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