Protective effects of pravastatin in murine lipopolysaccharide-induced acute lung injury.
1. The present study was designed to determine whether pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in BALB/c mice. 2. Acute lung injury was induced successfully by intratracheal administraiton of LPS (3 microg/g) in BALB/c mice. Pravastatin (3, 10 and 30 mg/kg, i.p.) was administered to mice 24 h prior to and then again concomitant with LPS exposure. 3. Challenge with LPS alone produced a significant increase in lung index and the wet/dry weight ratio compared with control animals. Pulmonary microvascular leakage, as indicated by albumin content in the bronchoalveolar lavage fluid (BALF) and extravasation of Evans blue dye albumin into lung tissue, was apparently increased in LPS-exposed mice. Lipopolysaccharide exposure also produced a significant lung inflammatory response, reflected by myeloperoxidase activity and inflammatory cell counts in BALF. Furthermore, histological examination showed that mice exposed to LPS also exhibited prominent inflammatory cell infiltration and occasional alveolar haemorrhage. 4. Pravastatin (3, 10 or 30 mg/kg, i.p.) produced a significant reduction in multiple indices of LPS-induced pulmonary vascular leak and inflammatory cell infiltration into lung tissue. Elevated tumour necrosis factor (TNF)-alpha levels in lung tissue homogenates of ALI mice were significantly decreased after administration of 10 or 30 mg/kg pravastatin. 5. These findings confirm significant protection by pravastatin against LPS-induced lung vascular leak and inflammation and implicate a potential role for statins in the management of ALI. The inhibitory effect of pravastatin was associated with its effect in decreasing TNF-alpha.
Yao
Hong-Wei
HW
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drugs Administration of China, Hangshou, People's Republic of China. yhgwei@hotmail.com
Mao
Lian-Gen
LG
Zhu
Jian-Ping
JP
D000418:Albumins / Q000032:analysis; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D019610:Cytoprotection / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D008070:Lipopolysaccharides; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D017035:Pravastatin / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000517:prevention & control*; D012129:Respiratory Function Tests; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000418:Albumins; D000924:Anticholesteremic Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D017035:Pravastatin