Mechanisms of toxic smoke inhalation and burn injury: Role of neutral endopeptidase and vascular leakage in mice

Autor:	Hal K. Hawkins, Sam Jacob, Daniel L. Traber, Robert A. Cox, David N. Herndon, Donald J. Deyo
Jazyk:	angličtina
Rok vydání:	2009
Předmět:	Male medicine.medical_specialty Burn injury Smoke Inhalation Injury Health Toxicology and Mutagenesis medicine.medical_treatment Smoke inhalation Phenylalanine Organophosphonates Poison control Pulmonary Edema Lung injury Toxicology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Internal medicine Neurogenic inflammation Medicine Animals Protease Inhibitors Saline neutral endopeptidase activity vascular permeability 030304 developmental biology Evans Blue 0303 health sciences business.industry medicine.disease plasma extravasation 3. Good health Mice Inbred C57BL Disease Models Animal Endocrinology chemistry acute lung injury NEP Anesthesia Neprilysin business Burns 030217 neurology & neurosurgery Research Article
Zdroj:	Toxicology Mechanisms and Methods
ISSN:	1537-6524 1537-6516
Popis:	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 h prior to SB injury (n = 5–8/group). Mice were anesthetized with i.p. ketamine/xylazine, intubated, and exposed to cooled cotton smoke (2 × 30 s). 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 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.
Databáze:	OpenAIRE
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