@article{ref1,
title="Mechanisms of Toxic Smoke Inhalation and Burn Injury: Role of Neutral Endopeptidase and Vascular Leakage in Mice",
journal="Toxicology mechanisms and methods",
year="2009",
author="Jacob, Sam and Deyo, Donald J. and Cox, Robert A. and Traber, Daniel L. and Hawkins, Hal K.",
volume="19",
number="3",
pages="191-196",
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.<p /><p>Language: en</p>",
language="en",
issn="1537-6516",
doi="10.1080/15376510902725649",
url="http://dx.doi.org/10.1080/15376510902725649"
}