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N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats.
Am J Physiol. 1997 Sep; 273(3 Pt 1):L548-55.AJ

Abstract

Although the antioxidant properties of N-acetylcysteine (NAC) in vitro are widely accepted, the efficacy of NAC in the prevention of O2 toxicity in vivo is poorly documented. The aim of our study was to investigate the presumed protective effect of NAC on hyperoxic lung injury, focusing on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Thirty-four male Wistar rats were divided in three groups (n = 10-14) and were exposed to air or to 60 or 85% O2 for 7 days. One-half of the rats in each group received 200 mg/kg NAC intraperitoneally one time per day from 3 days before exposure until the end of the experiment, and the other one-half received the vehicle. In the 85% O2-exposed animals, NAC led to more respiratory distress and weight loss. NAC did not prevent the rise in bronchoalveolar lavage lactate dehydrogenase and alkaline phosphatase, but it did prevent the rise in calculated ELF volume. NAC decreased GSH levels (1.4-fold) and gamma-GT activity (1.8-fold) in the air-exposed type II cells. In the 60% O2-exposed group, no effects of NAC were seen (except for a decrease in gamma-GT mRNA expression), but, in the 85% O2-exposed group, NAC gave rise to higher GSH (2.6-fold) and higher gamma-GT activity (2.9-fold) in the ELF and lower GSH (6.9-fold) and higher gamma-GT activity (3.6-fold) in the type II cells. Even in culture, GSH levels remained 1.5-fold lower than in the cells from the air-exposed animals and 2-fold lower than in the cells from the 85% O2-exposed animals. There was increased DNA damage (as assessed by thymidine incorporation) and apoptosis after hyperoxia, especially after 60% O2, and this effect was amplified after NAC treatment. Although protective at the endothelial side, NAC treatment led to adverse effects at the epithelial side, despite, or probably because of, restoration of the ELF GSH levels in the presence of high O2 levels. Because NAC is rapidly metabolized to cysteine, it is plausible that the effects of NAC are manifested through the toxic effects of cysteine.

Authors+Show Affiliations

Laboratory of Pneumology, Katholieke Universiteit Leuven, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9316488

Citation

van Klaveren, R J., et al. "N-acetylcysteine Does Not Protect Against Type II Cell Injury After Prolonged Exposure to Hyperoxia in Rats." The American Journal of Physiology, vol. 273, no. 3 Pt 1, 1997, pp. L548-55.
van Klaveren RJ, Dinsdale D, Pype JL, et al. N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats. Am J Physiol. 1997;273(3 Pt 1):L548-55.
van Klaveren, R. J., Dinsdale, D., Pype, J. L., Demedts, M., & Nemery, B. (1997). N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats. The American Journal of Physiology, 273(3 Pt 1), L548-55.
van Klaveren RJ, et al. N-acetylcysteine Does Not Protect Against Type II Cell Injury After Prolonged Exposure to Hyperoxia in Rats. Am J Physiol. 1997;273(3 Pt 1):L548-55. PubMed PMID: 9316488.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats. AU - van Klaveren,R J, AU - Dinsdale,D, AU - Pype,J L, AU - Demedts,M, AU - Nemery,B, PY - 1997/10/8/pubmed PY - 1997/10/8/medline PY - 1997/10/8/entrez SP - L548 EP - 55 JF - The American journal of physiology JO - Am. J. Physiol. VL - 273 IS - 3 Pt 1 N2 - Although the antioxidant properties of N-acetylcysteine (NAC) in vitro are widely accepted, the efficacy of NAC in the prevention of O2 toxicity in vivo is poorly documented. The aim of our study was to investigate the presumed protective effect of NAC on hyperoxic lung injury, focusing on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Thirty-four male Wistar rats were divided in three groups (n = 10-14) and were exposed to air or to 60 or 85% O2 for 7 days. One-half of the rats in each group received 200 mg/kg NAC intraperitoneally one time per day from 3 days before exposure until the end of the experiment, and the other one-half received the vehicle. In the 85% O2-exposed animals, NAC led to more respiratory distress and weight loss. NAC did not prevent the rise in bronchoalveolar lavage lactate dehydrogenase and alkaline phosphatase, but it did prevent the rise in calculated ELF volume. NAC decreased GSH levels (1.4-fold) and gamma-GT activity (1.8-fold) in the air-exposed type II cells. In the 60% O2-exposed group, no effects of NAC were seen (except for a decrease in gamma-GT mRNA expression), but, in the 85% O2-exposed group, NAC gave rise to higher GSH (2.6-fold) and higher gamma-GT activity (2.9-fold) in the ELF and lower GSH (6.9-fold) and higher gamma-GT activity (3.6-fold) in the type II cells. Even in culture, GSH levels remained 1.5-fold lower than in the cells from the air-exposed animals and 2-fold lower than in the cells from the 85% O2-exposed animals. There was increased DNA damage (as assessed by thymidine incorporation) and apoptosis after hyperoxia, especially after 60% O2, and this effect was amplified after NAC treatment. Although protective at the endothelial side, NAC treatment led to adverse effects at the epithelial side, despite, or probably because of, restoration of the ELF GSH levels in the presence of high O2 levels. Because NAC is rapidly metabolized to cysteine, it is plausible that the effects of NAC are manifested through the toxic effects of cysteine. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/9316488/N_acetylcysteine_does_not_protect_against_type_II_cell_injury_after_prolonged_exposure_to_hyperoxia_in_rats_ L2 - http://journals.physiology.org/doi/full/10.1152/ajplung.1997.273.3.L548?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -