Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species are a major cause of damage occurring in ischemic tissue after reperfusion. During reperfusion transitional metals such as iron are required for reactive oxygen species to mediate their major toxic effects. Xanthine oxidase is an important source of reactive oxygen species during ischemia-reperfusion injury, but not in all organs or species. Because cytochrome P-450 enzymes are an important pulmonary source of superoxide anion (O2-.) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical (.OH) formation and propagation of lipid peroxidation, we postulated that cytochrome P-450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P-450 enzymes in a rabbit model of reperfusion lung injury. The P-450 inhibitors 8-methoxypsoralen, piperonyl butoxide, and cimetidine markedly decreased lung edema from transvascular fluid flux. Cimetidine prevented the reperfusion-related increase in lung microvascular permeability, as measured by movement of 125I-albumin from the vascular space into lung water and alveolar fluid. P-450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P-450 inhibitors did not block enhanced O2-. generation by ischemic reperfused lungs, measured by in vivo reduction of succinylated ferricytochrome c in lung perfusate, but did prevent the increase in non-protein-bound low molecular weight chelates of iron after reperfusion. Thus, cytochrome P-450 enzymes are not likely a major source of enhanced O2-. generation, but serve as an important source of iron in mediating oxidant injury to the rabbit lung during reperfusion. These results suggest an important role of cytochrome P-450 in reperfusion injury to the lung and suggest potential new therapies for the disorder.
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PMID:Role of cytochrome P-450 in reperfusion injury of the rabbit lung. 217 18

An animal model utilizing gamma imaging was used to examine pulmonary edema of an inhalation injury model. Tests were conducted using radiolabeled tracers and a dual indicator dilution technique as well as gravimetric analysis of excised lungs to determine extravascular water formation. The effect of cimetidine (Tagamet, an H2 receptor antagonist) was investigated as a potential agent for reduction of pulmonary edema following inhalation injury. Control groups included no treatment; smoke only; fluids only; and smoke and fluids. These were compared with identical groups given the same treatments but with the addition of cimetidine (100-150 mg/kg body weight intravenously). Fluids administered were 5% body weight intravenous infusions of lactated Ringer's solution over two hours. Results show that pulmonary edema was evidenced in animals given an inhalation injury, and was markedly worsened by fluid resuscitation. Treatment with cimetidine at high doses, either before or after inhalation injury, did not protect the animals from formation of pulmonary edema.
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PMID:Effect of high-dose cimetidine on pulmonary extravascular water after acute smoke inhalation injury. 282 76