Effects of free radical scavengers, methylprednisolone, and ulinastatin on acute xanthine and xanthine oxidase-induced lung injury in rats.
We investigated the role of free radicals, especially from activated neutrophils, in acute xanthine and xanthine oxidase-induced lung injury in rats. We evaluated the effects of intravenously administered intracellular and extracellular free radical scavengers (for O2-., H2O2, and .OH), methylprednisolone (MP), and Ulinastatin (UST, a protease inhibitor), on this animal model of lung injury. At 5 min prior to the intrabronchial injection of a mixture of xanthine (X, 100 nmol) and xanthine oxidase (XO, 1 unit) used to induce unilateral lung damage, rats were pretreated intravenously with superoxide dismutase (SOD, 40 mg/kg), SOD (40 mg/kg) plus catalase (CAT, 30 mg/kg), dimethylthiourea (DMTU, 500 mg/kg), N-2-mercaptopropionyl glycine (MPG, 20 mg/kg), MP, 30 mg/kg, and UST, 50,000 units/kg. Each scavenger was infused intravenously at one-half the initial dose for 20 min after intrabronchial injection; 3 hr later, we examined the wet/dry lung weight ratios and the levels of thiobarbituric acid-reactive substances (TBARS) in lung tissue. Intrabronchial injection of the X/XO mixture markedly increased wet/dry lung weight ratios and lung tissue content of TBARS. Histopathologic changes were observed in the injected lung as well. Pretreatment with SOD + CAT, DMTU, and UST significantly reduced the increases in wet/dry lung weight ratios and lung tissue content of TBARS induced by the intrabronchial injection of the X/XO mixture. Our data suggest indirectly that free radicals (H2O2, .OH) and proteases from activated neutrophils may contribute, in part, to the lung damage induced by the O2-.-generating system of xanthine and xanthine oxidase.
Department of Anesthesiology, Nippon Medical School, Tokyo, Japan.
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Cai
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Ogawa
D000818:Animals; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006023:Glycoproteins / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase; D014970:Xanthines
D016166:Free Radical Scavengers; D006023:Glycoproteins; D017392:Thiobarbituric Acid Reactive Substances; D014970:Xanthines; D019820:Xanthine; D014969:Xanthine Oxidase; C028665:urinastatin; D008775:Methylprednisolone