N-acetylcysteine increases the glutathione content and protects rat alveolar type II cells against paraquat-induced cytotoxicity.
A protective effect of N-acetylcysteine in oxidative lung damage was reported by a number of workers; however, the mechanism underlying this effect was not thoroughly elucidated. The present research investigates the protection by N-acetylcysteine against paraquat-induced cytotoxicity to alveolar type II cells, which are known to be specific targets of paraquat toxicity in vivo. We found that addition of 1 mM N-acetylcysteine to alveolar type II cells incubated with 1 mM paraquat reduced the cytotoxic index from 17.4 +/- 1.3% to 9.3 +/- 1.5%. This effect could not be explained by the interference of N-acetylcysteine with the active uptake of paraquat by type II cells. Incubation of these cells with N-acetylcysteine enhances their glutathione content, thus reducing the paraquat- induced depletion of glutathione in these cells. These results suggest that N-acetylcysteine exerts its protective effect by acting as a precursor for glutathione in alveolar type II cells.
Hoffer
E
E
Israel Poison Information Center, Rambam Medical Center and Faculty of Medicine, Technion, Haifa, Israel.
Baum
Y
Y
Tabak
A
A
Taitelman
U
U
D000111:Acetylcysteine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D010269:Paraquat / Q000378:metabolism / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
D005978:Glutathione; D010269:Paraquat; D000111:Acetylcysteine