Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery.

Abstract

INTRODUCTION:

Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice.

METHODS:

Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined.

RESULTS:

Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-β and c-KIT in imatinib or nilotinib group were significantly lower than LPS group.

CONCLUSIONS:

Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.

• Authors: In Kyoung Kim, Chin Kook Rhee, Chang Dong Yeo, Hyeon Hui Kang, Dong Gun Lee, Sang Haak Lee, Jin Woo Kim
• Journal: Critical care (London, England) (Crit Care) Vol. 17 Issue 3 Pg. R114 (Jun 20 2013) ISSN: 1466-609X [Electronic] England
• PMID: 23787115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Lipopolysaccharides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate
• Protein-Tyrosine Kinases
• nilotinib

Topics

• Acute Lung Injury (chemically induced, drug therapy, enzymology)
• Animals
• Benzamides (pharmacology, therapeutic use)
• Disease Models, Animal
• Female
• Imatinib Mesylate
• Lipopolysaccharides (toxicity)
• Mice
• Mice, Inbred ICR
• Neutropenia (drug therapy, enzymology)
• Piperazines (pharmacology, therapeutic use)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Pyrimidines (pharmacology, therapeutic use)
• Random Allocation
• Recovery of Function (drug effects, physiology)
• Treatment Outcome