Attenuation by 2,3-dihydroxybenzoic acid of acute lung injury induced by cobra venom factor in the rat.
Neutrophil-derived oxygen metabolites are thought to play an important role in the genesis of acute lung injury in a variety of diseases. In an effort to find an agent that might limit the injury, we evaluated the beneficial effects of 2,3-dihydroxybenzoic acid (DHB), a drug that has been safely administered to humans as an iron-chelating agent. Because experimental evidence has demonstrated that DHB can act as an inhibitor of free radical-induced reactions, we tested its protective effect against the neutrophil-dependent lung injury that occurs in rats after the intravenous infusion of cobra venom factor (CVF). Using a permeability index that measures the amount of intravenously administered 125I-albumin that accumulates in lung tissue, we found that pretreatment with DHB reduced (p less than 0.05) the lung injury in CVF-treated rats in a dose-dependent manner. Morphometric analysis of lung tissue indicated that the protection by DHB was not caused by inhibition of CVF-induced neutrophil sequestration within the lung vasculature. Because iron-saturated DHB did not attenuate lung injury, and because in vitro experiments demonstrated that DHB inhibited iron-hydrogen peroxide-induced peroxidation of phospholipid liposomes, we suspect that DHB may be protecting the lung via chelation of iron. We conclude that dihydroxybenzoic acid protects the rat lung from the neutrophil-dependent lung injury that occurs after cobra venom factor infusion. Because this drug has been safely administered to humans, it may have potential as an agent to prevent acute lung injury.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms; D062385:Hydroxybenzoates / Q000627:therapeutic use*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D007958:Leukocyte Count; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000648:ultrastructure; D008171:Lung Diseases / Q000139:chemically induced / Q000517:prevention & control*; D009504:Neutrophils; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains
D004546:Elapid Venoms; D062385:Hydroxybenzoates; D007502:Iron Chelating Agents; D008054:Lipid Peroxides; C016310:cobra venom factor; C009135:2,3-dihydroxybenzoic acid