Citation

Jacob S, Deyo DJ, Cox RA, Traber DL, Hawkins HK. Toxicol. Mech. Methods 2009; 19(3): 191-196.

Affiliation

Department of Pathology, University of Texas Medical Branch, Galveston, Texas.

Copyright

(Copyright © 2009, Informa Healthcare)

DOI

10.1080/15376510902725649

PMID

19727335

PMCID

PMC2736052

Abstract

The effects of neutral endopeptidase (NEP) in acute inflammation in the lung were studied using a newly developed murine model of smoke and burn (SB) injury. C57BL/6 mice were pretreated with an i.v. dose of a specific NEP antagonist CGS-24592 (10 mg/Kg) 1 hr prior to SB injury (n = 5 to 8/group). Mice were anesthetized with i.p. ketamine/xylazine, intubated and exposed to cooled cotton smoke (2X 30 sec). After s.c. injection of 1 ml 0.9% saline, each received a 40% total body surface area (TBSA) flame burn. Buprenorphene (2 mg/kg) was given i.p. and resuscitated by saline. Evans Blue dye (EB) was injected i.v. 15 min before sacrifice. Lung wet/dry weight ratio was measured. After vascular perfusion, lungs were analyzed for their levels of EB dye and myeloperoxidase (MPO). In mice pretreated with CGS-24592 followed by SB injury the EB levels were significantly higher (61%, p = 0.043) than those with SB injury alone. There was a significant increase (144%, p = 0.035) in EB dye in animals with SB injury alone as compared to shams. In mice pretreated with CGS-24592 prior to SB injury wet/dry weight ratios were significantly (27%, p = 0.042) higher as compared to animals with SB injury alone. CGS-24592 pretreatment also caused a significant increase in MPO (29%, p = 0.026) as compared to mice with SB injury alone. In conclusion the current study indicates that specific NEP inhibitor CGS 24592 exacerbates the SB induced lung injury and inflammation in mice.

Language: en