N-acetylcysteine delays the infiltration of inflammatory cells into the lungs of paraquat-intoxicated rats.
We investigated a possible role for N-acetylcysteine (NAC), a well-known antioxidant and free radical scavenger, against oxidative lung damage as observed in the in vivo model of paraquat-intoxicated rats. The administration of two ip doses of 50 mg/kg NAC to paraquat-intoxicated animals did not change the glutathione status of the lungs, as determined by the measurement of nonprotein sulfhydryl (NP-SH) groups. The administration of NAC did however suppress the paraquat-induced release of chemoattractants for neutrophils in the bronchoalveolar fluid when the lavage was carried out 12 hr after the administration of 30 mg/kg paraquat. Also, in the intoxicated NAC-treated animals, the infiltration of inflammatory cells was significantly reduced, as demonstrated by the examination of the cell composition of the bronchoalveolar lavage (BAL), 24 hr after paraquat. Phorbol myristate acetate-stimulated superoxide anion production from the AM isolated from the BAL of paraquat-intoxicated nontreated animals was lower than that of controls, whereas in the NAC-treated animals, it was close to that of the controls. The obtained results indicate that NAC has a protective effect against oxidative lung damage by delaying inflammation. It also prevents the paraquat-induced reduction of superoxide anion production by stimulated AM. In the present model, however, the NAC administration regimen did not affect the survival rate of paraquat-intoxicated rats.
Israel Poison Information Center, Haifa.
E
E
Hoffer
I
I
Avidor
O
O
Benjaminov
L
L
Shenker
A
A
Tabak
A
A
Tamir
D
D
Merzbach
U
U
Taitelman
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control; D008099:Liver / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D002630:Chemotactic Factors; D013438:Sulfhydryl Compounds; D013481:Superoxides; D010269:Paraquat; D000111:Acetylcysteine