PROTECTIVE EFFECTS OF PRAVASTATIN IN MURINE LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY
Version of Record online: 10 AUG 2006
Clinical and Experimental Pharmacology and Physiology
Volume 33, Issue 9, pages 793–797, September 2006
How to Cite
Yao, H.-W., Mao, L.-G. and Zhu, J.-P. (2006), PROTECTIVE EFFECTS OF PRAVASTATIN IN MURINE LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY. Clinical and Experimental Pharmacology and Physiology, 33: 793–797. doi: 10.1111/j.1440-1681.2006.04440.x
- Issue online: 10 AUG 2006
- Version of Record online: 10 AUG 2006
- Received 26 December 2005; revised 12 February 2006; accepted 13 February 2006.
- acute lung injury;
- 1The 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.
- 2Acute lung injury was induced successfully by intratracheal administraiton of LPS (3 mg/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.
- 3Challenge 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.
- 4Pravastatin (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)-a levels in lung tissue homogenates of ALI mice were significantly decreased after administration of 10 or 30 mg/kg pravastatin.
- 5These 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-a.