title: [Endotoxin-induced lung injury. The roles of leukocytes and oxidants, and the efficacies of steroids and antioxidants].
abstract: Previous work in our laboratory has shown the relation between leukocytes (WBC) and the generation of oxidants in endotoxin (LPS) shock. The purpose of this study was to find out if WBC-derived oxidants can produce acute lung injury in guinea pigs given LPS. We alos evaluated the efficacies of steroids and antioxidants against the initial changes in LPS-induced lung injury. One group of guinea pigs (200-250 g, male) received 0.7 mg/kg (LD50, 24 hrs.) of E. coli LPS in the peritoneal cavity (group I). The animals in group II received 30 mg/kg of methylprednisolone (MP), followed by intraperitoneal LPS. The animals in group III were given 30 mg/kg of 2-aminomethyl-4-tert-butyl-6-propionylphenol hydrochloride (ONO-3144), a known as antioxidant (OH radical scavenger), and then an injection of LPS. The animals were killed at following time course: 30, 60 or 180 minutes after the LPS injection. Hematological examinations (WBC counts), total cell counts and differential counts in bronchoalveolar lavage (BAL) fluid were done along with light microscopic studies. Superoxide dismutase (SOD) activity, catalase activity and malonaldehyde (MDA) produced as a result of lipid peroxidation in the lung were measured and correlated with histological changes. Survival ratios of the three groups were compared. The results obtained were: 1) Significant leukopenia occurred in all groups. 2) In group I, WBC, especially eosinophils, were recovered by BAL and the total cell number of the BAL fluid had increased by 180 minutes after LPS injection, but MP or ONO-3144 treatment inhibited the migration of WBC (eosinophils and neutrophils) into alveolar lumen after LPS injection. 3) Histologic examinations revealed diffuse edema, hemorrhage, and marked leukocyte infiltration in the alveoli in group I, but not in group II or III. 4) SOD activity in all group diminished below the control level. Catalase activity had significantly increased by 180 minutes after LPS injection in group I, but not in group II or III. MDA had increased remarkably by 60 minutes after injection of LPS in group I, but MP or ONO-3144 treatment prevented such increases. 5) Animals in group II and III survived significantly longer than those in the other group. In conclusion, these findings suggest that LPS provokes WBC-mediated vascular damage in the lung and steroids or antioxidants can minimize the injury and prevent edema formation. Steroids might be useful for achieving quantifiable changes in LPS-induced WBC chemotaxis to the lung and for decreasing oxidant-induced lung injury.
authors.affiliation: First Department of Surgery, Nippon Medical School, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: M M
authors.initials: MM
authors.lastname: Onda
authors.forename: M
authors.initials: M
authors.lastname: Miyashita
authors.forename: N
authors.initials: N
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006168:Guinea Pigs; D007958:Leukocyte Count; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D016877:Oxidants / Q000378:metabolism; D011427:Propiophenones / Q000008:administration & dosage*; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D012772:Shock, Septic / Q000150:complications* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D011427:Propiophenones; C037467:2-aminomethyl-4-tert-butyl-6-propionylphenol; D013482:Superoxide Dismutase; D008775:Methylprednisolone