Effects of free radical scavengers, methylprednisolone, and ulinastatin on acute xanthine and xanthine oxidase-induced lung injury in rats.

Abstract

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.

• Authors: M Cai, R Ogawa
• Journal: Circulatory shock (Circ Shock) Vol. 43 Issue 2 Pg. 71-8 (Jun 1994) ISSN: 0092-6213 [Print] United States
• PMID: 7834823 (Publication Type: Journal Article)

Chemical References

• Free Radical Scavengers
• Glycoproteins
• Thiobarbituric Acid Reactive Substances
• Xanthines
• Xanthine
• Xanthine Oxidase
• urinastatin
• Methylprednisolone

Topics

• Animals
• Disease Models, Animal
• Free Radical Scavengers (administration & dosage)
• Glycoproteins (administration & dosage)
• Infusions, Intravenous
• Lung (drug effects, pathology)
• Male
• Methylprednisolone (administration & dosage)
• Organ Size
• Rats
• Rats, Wistar
• Respiratory Distress Syndrome (chemically induced, metabolism, pathology, prevention & control)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Xanthine
• Xanthine Oxidase
• Xanthines