Protective effect of pravastatin on lipopolysaccharide-induced acute lung injury during neutropenia recovery in mice.

Abstract

Although neutropenia recovery is associated with deterioration of preexisting acute lung injury (ALI), there are few reports of the preventive strategies. Statins have been found to attenuate inflammatory responses in murine models of lipopolysaccharide (LPS)-induced ALI. The aim of this study was to determine whether pravastatin could attenuate ALI during neutropenia recovery in mice. Cyclophosphamide was administered to mice to induce neutropenia. Mice were given intratracheal LPS 7 days after cyclophosphamide administration, after which pravastatin was administered by intraperitoneal injection. In order to study the effects of pravastatin, mice were killed on day 5. Pravastatin attenuated the pulmonary edema and histopathological changes of LPS-induced lung injury. The accumulation of neutrophils and the concentrations of TNF-α, IL-1β, IL-6, and MPO in BAL fluids were also effectively inhibited by pravastatin. The expression levels of Toll-like receptor 4, nuclear factor kappa B, tumor growth factor-β and matrix metalloproteinase-9 were significantly reduced by pravastatin. Taken together, pravastatin significantly attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the potential of pravastatin in the treatment of ALI during neutropenia recovery.

• Authors: Chang Dong Yeo, Chin Kook Rhee, In Kyoung Kim, Hyeon Hui Kang, Sang Haak Lee, Sook Young Lee, Soon Seok Kwon, Young Kyoon Kim, Kwan Hyoung Kim, Jin Woo Kim
• Journal: Experimental lung research (Exp Lung Res) Vol. 39 Issue 2 Pg. 99-106 (Mar 2013) ISSN: 1521-0499 [Electronic] England
• PMID: 23368428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Immunosuppressive Agents
• Interleukin-1beta
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Cyclophosphamide
• Pravastatin

Topics

• Acute Lung Injury (chemically induced, etiology, prevention & control)
• Animals
• Bronchoalveolar Lavage Fluid
• Cyclophosphamide (pharmacology)
• Disease Models, Animal
• Female
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Immunosuppressive Agents (pharmacology)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Lipopolysaccharides (pharmacology)
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Neutropenia (chemically induced, complications, drug therapy)
• Pravastatin (pharmacology)
• Pulmonary Edema (chemically induced, etiology, prevention & control)
• Respiratory Distress Syndrome (chemically induced, etiology, prevention & control)
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)