n-monoacetylcystine and Lung-Diseases

Topics: Acute Disease; Antioxidants; Capillary Permeability; Cell Adhesion Molecules; Cystine; Eosinophils; Humans; Lung Diseases; Lung Diseases, Interstitial; NF-kappa B; Oxidants; Pulmonary Circulation

The purpose of this study was to investigate the effects of NAC (N-acetylcysteine) on endotoxin induced acute lung injury in unanesthetized sheep. The results showed that NAC attenuated the responses to endotoxemia, and the rise in pulmonary artery pressure was significantly diminished, and the rise of TXB2 and 6-keto-PGF1 alpha in plasma and lung lymph was less significantly for NAC + E than for E alone. The QL (lung lymph flow), PC (lung lymph protein clearance) and PS (pulmonary capillary surface permeability area) were significantly decreased in NAC + E group. The lipid peroxide contents in artery plasma and lung lymph were not increased in NAC-treated group. We conclude that NAC is capable of attenuating all pathophysiologic changes after endotoxin infusion, blocking the reaction of oxygen free radicals, and protecting lungs from oxidant damage.

Topics: Animals; Cystine; Endotoxins; Escherichia coli; Female; Lipid Peroxides; Lung Diseases; Lymph; Sheep; Toxemia

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.

Topics: Acrolein; Administration, Inhalation; Aldehydes; Animals; Cystine; Disease Models, Animal; Injections, Intravenous; Lung Diseases; Methylprednisolone; Organ Size; Oxygen; Rats; Rats, Inbred Strains