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

Sam Jacob, Donald J. Deyo, Robert A. Cox, Daniel L. Traber, David Herndon, Hal K. Hawkins

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 h prior to SB injury (n 58/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.

Original languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalToxicology Mechanisms and Methods
Volume19
Issue number3
DOIs
StatePublished - 2009

Fingerprint

Inhalation Burns
Smoke Inhalation Injury
Neprilysin
Poisons
Smoke
Blood Vessels
Evans Blue
Coloring Agents
Wounds and Injuries
Peroxidase
Pneumonia
Animals
Xylazine
Weights and Measures
Body Surface Area
Ketamine
Lung Injury
Pulmonary Edema
Protease Inhibitors
Inbred C57BL Mouse

Keywords

  • Acute lung injury
  • NEP
  • Neurogenic inflammation
  • Neutral endopeptidase activity
  • Plasma extravasation
  • Vascular permeability

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Mechanisms of toxic smoke inhalation and burn injury : Role of neutral endopeptidase and vascular leakage in mice. / Jacob, Sam; Deyo, Donald J.; Cox, Robert A.; Traber, Daniel L.; Herndon, David; Hawkins, Hal K.

In: Toxicology Mechanisms and Methods, Vol. 19, No. 3, 2009, p. 191-196.

Research output: Contribution to journalArticle

Jacob, Sam ; Deyo, Donald J. ; Cox, Robert A. ; Traber, Daniel L. ; Herndon, David ; Hawkins, Hal K. / Mechanisms of toxic smoke inhalation and burn injury : Role of neutral endopeptidase and vascular leakage in mice. In: Toxicology Mechanisms and Methods. 2009 ; Vol. 19, No. 3. pp. 191-196.
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