HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Leukotoxin-diol: a putative toxic mediator involved in acute respiratory distress syndrome.

Abstract
Leukotoxin is clinically associated with acute respiratory distress syndrome (ARDS). Recently, we found that leukotoxin-diol, the hydrated product of leukotoxin, is more toxic than the parent leukotoxin in vitro (Moghaddam and colleagues, Nature Med. 1997;3:562-566). To test if this difference in the toxicity of leukotoxin and leukotoxin-diol exists in vivo, Swiss Webster mice were administered leukotoxin or leukotoxin-diol. All mice treated with leukotoxin-diol died of ARDS-like respiratory distress, whereas the animals exposed to leukotoxin at the same dose survived. Histopathologic evaluation of the lungs revealed massive alveolar edema and hemorrhage with interstitial edema around blood vessels in the lungs of mice treated with leukotoxin-diol, whereas the lungs of mice treated with identical doses of leukotoxin had perivascular edema only and little change in alveolar spaces. Immunohistochemistry showed that the soluble epoxide hydrolase responsible for the hydrolysis of leukotoxin to its diol is concentrated in the vascular smooth muscle of small and medium-sized pulmonary vessels. In addition, 4-phenylchalcone oxide, an inhibitor of soluble epoxide hydrolase, was found to decrease the mortality induced by leukotoxin but had no effect on mortality induced by leukotoxin-diol. These studies provide strong in vivo evidence that leukotoxin may act as a protoxicant and that the corresponding diol is a putative toxic mediator involved in the development of ARDS.
AuthorsJ Zheng, C G Plopper, J Lakritz, D H Storms, B D Hammock
JournalAmerican journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 25 Issue 4 Pg. 434-8 (Oct 2001) ISSN: 1044-1549 [Print] United States
PMID11694448 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • 4-phenylchalcone oxide
  • 9,10-dihydroxy-12-octadecenoic acid
  • Chalcones
  • Enzyme Inhibitors
  • Exotoxins
  • Stearic Acids
  • leukotoxin
  • Chalcone
  • Epoxide Hydrolases
Topics
  • Animals
  • Chalcone (analogs & derivatives, pharmacology)
  • Chalcones
  • Dose-Response Relationship, Drug
  • Edema (chemically induced)
  • Enzyme Inhibitors (pharmacology)
  • Epoxide Hydrolases (antagonists & inhibitors, drug effects, metabolism)
  • Exotoxins (toxicity)
  • Lung (drug effects, pathology)
  • Male
  • Mice
  • Respiratory Distress Syndrome (chemically induced, mortality, pathology)
  • Stearic Acids (toxicity)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: