The antioxidative action of dexamethasone and its protective effect on acute lung injury induced by lipopolysaccharide in rabbits

Objective To explore the effect of dexamethasone (DEX) on acute lung injury induced by lipopolysaccharide (LPS) and the mechanism of the action. Methods The rabbit model was prepared by giving an intravenous injection of LPS (3 μg/kg) initially and by giving an infusion of LPS (50 μg/kg, within 2 h) on the next day. When the pulmonary dynamic compliance(Cdyn)dropped to 75% of the baselevel, the rabbits were randomly allocated into 3 groups (n=8 each). The DEX group was treated with DEX 1 mg/kg iv, the control (CON) group with 0.9% NaCl 0.2 ml/kg iv, while the 75% Cdyn group was studied before starting any treatment. The activities of superoxide dismutase (SOD) and xanthine oxidase (XOD), and nitrite/nitrate (NO- 2/NO- 3) in the blood were determined. Six h after the treatment, the animals were killed to separate the lung tissue for measurement of XOD and myeloperoxidase (MPO) and for histological examination. Results The activities of lung XOD and MPO were significantly decreased in DEX group (P0.05 and P0.01 respectively). The activity of XOD and the level of NO were decreased in the DEX group (P0.05), while the activity of plasma SOD was higher in DEX group than in CON group (P0.05). The degrees of tissue injury and inflammatory reactions in the pulmonary stroma and alveoli were much less in the DEX group than those in the CON group. Conclusions Dexamethasone (1 mg/kg) has protective effects on the development of acute lung injury induced by LPS in rabbits. This action may be related to the inhibition of NO production and lipid peroxidation and the enhancement of tissues′ antioxidative activity.