N-acetylcysteine ameliorates hyperoxic lung injury in the preterm guinea pig.
The therapeutic efficacy of N-acetylcysteine (NAC) in the management of hyperoxia-induced lung injury was assessed using the preterm guinea pig model of prematurity. Preterm guinea pig pups were delivered by Caesarean section 3 days preterm, and exposed to either 21 or 95% oxygen for 72 hr. NAC (200 mg/kg body weight) or saline was injected twice daily. Bronchoalveolar lavage fluid (BALF) from hyperoxia-exposed pups contained significantly higher protein concentrations and an increased number of neutrophils. NAC partly ameliorated lung injury, preventing the increase in BALF protein concentration, which is generally associated with oedema. There was no effect on the movement of neutrophils into the lung airspaces in response to oxygen. Treatment with NAC had no effect on lung or liver glutathione (reduced) (GSH) concentrations either after 2 hr post-administration, or over the full 72 hr experimental period. An apparent resistance of the lung to increased synthesis or uptake of GSH was demonstrated by the lack of effect of direct administration of GSH, its isopropyl ester or 2-oxo-4-thiazolidine carboxylic acid. Oxygen exposure alone (95%) increased lung concentrations by 60-70%. It would, therefore, appear from this data that NAC may have potential as a future component of antioxidant therapy, although its effects are not mediated through increased GSH levels.
Langley
S C
SC
Rayne Institute, St Thomas' Hospital, London, U.K.
Kelly
F J
FJ
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000517:prevention & control*; D010100:Oxygen / Q000633:toxicity*; D011506:Proteins / Q000032:analysis; D012122:Ventilators, Mechanical / Q000009:adverse effects
D011506:Proteins; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D010100:Oxygen; D000111:Acetylcysteine