Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage.
Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. We evaluated NAC and methylprednisolone in two rat models of inhalational injury: 40-hr exposure to greater than 97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). For oxygen toxicity, NAC (80 mg) or methylprednisolone (10 mg) were given IP every 2 or 6 hr, respectively. For acrolein, single doses of NAC (1 g/kg) and methylprednisolone (30 mg/kg) were given intravenously 15 min before exposure. In sham-exposed control animals, neither treatment favorably effected mortality, lung wet/dry weight ratios, or pulmonary histology. The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. We caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.
Critchley
J A
JA
Department of Clinical Pharmacology, University of Edinburgh, UK.
Beeley
J M
JM
Clark
R J
RJ
Summerfield
M
M
Bell
S
S
Spurlock
M S
MS
Edginton
J A
JA
Buchanan
J D
JD
D000171:Acrolein / Q000008:administration & dosage / Q000633:toxicity*; D000280:Administration, Inhalation; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D003553:Cystine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D000447:Aldehydes; D003553:Cystine; D000171:Acrolein; D010100:Oxygen; D008775:Methylprednisolone; C030905:N-monoacetylcystine