Protection against pulmonary O2 toxicity by N-acetylcysteine

Abstract

N-acetylcysteine (NAC) is a known antioxidant. We therefore investigated NAC as an agent protective against O2 toxicity in the lung. Twelve dogs were anaesthetized with sodium pentobarbital and ventilated with 100% O2 for 54 h. Five were given diluent and 7 intravenous NAC (loading dose prior to 100% O2 ventilation of 150 mg.kg-1 and maintenance dose of 20 mg.kg-1.h-1). Every 6 h, physiological evaluation of the pulmonary circulation, mechanical properties, and gas exchange was performed. Post-mortem evaluation consisted of gross examination and weighing followed by light and electron microscopy. By both functional and structural criteria, NAC protected against the effects of 100% O2. The NAC group developed significantly less increase in pulmonary vascular resistance, arterial carbon dioxide tension (PaCO2) and lung wet weight, while dynamic compliance was greater. NAC also delayed the development of abnormal ventilation-perfusion relationships and was associated with reduced pulmonary white cell accumulation, with less evidence of alveolar and interstitial oedema. NAC may well be worthy of evaluation as a therapeutic agent in human diseases characterized by oxidant damage.

Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages

“…~he aim of this study was to determine if NAC given in vivo resulted in increased glutathione biosynthesis, thereby preventing free radical generation as suggested in recent reports [29,30). However, in this study we have employed specific assays to detect nanomole amounts of Hz0 2 and o;, whereas many of the previously published studies which have investigated the role of NAC as an antioxidant have used the less specific chemiluminescence assay (11,14,27].…”

Protection by N-acetylcysteine against pulmonary endothelial cell damage induced by oxidant injury

“…In recent years, increasing interest has arisen in Nacetylcysteine (NAC) as a potential therapeutic agent in oxidant-mediated disorders [10][11][12]. This compound, which has been widely used as a mucolytic drug for the treatment of chronic obstructive lung diseases [13][14][15], is a potent antioxidant agent, showing protective effects in several models of lung injury [16,17]. The antioxidant activity of NAC appears to be related to at least two mechanisms, i.e.…”