Função pulmonar, estresse oxidativo e marcadores inflamatórios na lesão pulmonar aguda induzida por lipopolissacarídeo: diferentes efeitos da atorvastatina, pravastatina e simvastatina

Abstract

To determinate what statins could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in C57BL/6 mice. Young male mice (± 23 g) were divided into 5 groups (n=6 each): injected with LPS i.p. (10 mg/kg), LPS plus atorvastatin (10 mg/kg/day; LPS+A group) or pravastatin (5 mg/kg/day; LPS+P group) or simvastatin (20 mg/kg/day; LPS+S group). Control group received saline (i.p.). In a separated group of mice (n=5) the sum of pulmonary resistive and viscoelastic pressures (DeltaPtot) and static elastance (E[st]) were measured. One day later (24 h), the animals were sacrificed, BAL performed and lungs were removed for histopathological analysis and homogenized for biochemical analyses (ELISA, catalase, superoxide dismutase, myeloperoxidase, thiobarbituric acid reactive substances, protein carbonyls and griess assay). The amount of leukocytes was lower in LPS+P (p<0.01) and LPS+S (p<0.05). Cytokine levels of MCP-1 was lower in LPS+P (p<0.01) while IL-6 was lower in LPS+P (p<0.01) and LPS+S (p <0.05). Redox markers (superoxide dismutase and catalase) were lower in LPS+A (p<0.01). Lipid peroxidation (malondialdehyde and hydroperoxides) were lower in all treated groups (p<0.05). Myeloperoxidase was lower in LPS+P (p<0.01). DeltaPtot and E(st) were significantly higher in the LPS group than in the other groups. Our results suggest that atorvastatin and pravastatin, but no simvastatin, exhibits anti-inflammatory and antioxidant actions in LPS-induced ALI.