Cimetidine reduces hyperoxic lung injury in lambs.

摘要: We previously reported that pretreatment with endotoxin significantly reduced acute pulmonary O2 toxicity in lambs (J. Appl. Physiol. 65: 1579-1585, 1988). One of endotoxin's many effects is to inhibit cytochrome P-450 mono-oxygenation reactions, which are believed produce toxic species. Therefore, one possible explanation for beneficial effect it inhibited P-450-mediated radical production during hyperoxia. To test this hypothesis, we administered a single dose cimetidine, noncompetitive inhibitor activity, nine before continuous exposure greater than 95% O2. Compared six control O2-exposed lambs, the cimetidine-treated maintained normal gas exchange longer period time (P less 0.01), accumulated lung water at slower rate and had microvascular permeability after 72 h exposure. Postmortem levels antioxidant enzymes blood-free homogenate were not increased lambs. However, oxidized glutathione lower ratio concentrations (GSH/GSSG ratio) was sevenfold higher measured 0.001). In four ranitidine (a drug chemically related cimetidine but without inhibitory activity) no either on course injury or postmortem antioxidants. Microsomes isolated from all study animals activity form 2 isozyme measured.(ABSTRACT TRUNCATED AT 250 WORDS)