Modulation of oxidant lung injury by using liposome-entrapped superoxide dismutase and catalase.
Increased cellular generation of partially reduced species of oxygen mediates the toxicity of hyperoxia to cultured endothelial cells and rats exposed to 95-100% oxygen. Liposomal entrapment and intracellular delivery of superoxide dismutase (SOD) to cultured porcine aortic endothelial cells increased the specific activity of cellular SOD up to 15-fold. The liposome-mediated augmentation of SOD activity persisted in cell monolayers and rendered these cells resistant to oxygen-induced injury in a cell SOD activity-dependent manner. Addition of free SOD to culture medium had no effect on cell SOD activity or resistance to oxygen toxicity. SOD and catalase-containing liposomes injected i.v. into rats increased lung-associated enzyme specific activities two- to fourfold. Liposome entrapment of both SOD and catalase significantly increased the circulating half-lives of these enzymes and was critical for prevention of in vivo oxygen toxicity. Free SOD and catalase injected i.v. in the absence or presence of control liposomes did not increase corresponding lung enzyme activities or survival time in 100% oxygen. These studies show that O2- and H2O2 are important mediators of oxygen toxicity and that intracellular delivery of oxygen protective enzymes can reduce tissue injury owing to overproduction of partially reduced oxygen species.
D000818:Animals; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D010996:Pleural Effusion / Q000209:etiology; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D013552:Swine
D005609:Free Radicals; D008081:Liposomes; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen