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Requirements for neutrophil products and L-arginine in ischemia-reperfusion injury.

Abstract
Ischemia followed by reperfusion in rat limb results in evidence of vascular injury in the limb as well as in the lung as measured by leakage of [125I]albumin and extravasation of [51Cr] red blood cells. Vascular injury in lung and limb was proportional to the time of limb reperfusion and was associated with accumulation of myeloperoxidase, as well as evidence of complement consumption. In this model, the rank order of protective interventions was: neutrophil depletion > catalase + superoxide dismutase = allopurinol > dimethylthiourea = dimethylsulfoxide > deferoxamine = complement depletion. These data suggest that toxic oxygen products of neutrophils are related to the development of vascular injury. There was a reasonable correlation between protective effects of interventions and reduced tissue content of myeloperoxidase. Systemic treatment with the L-arginine antagonists, NG-monomethyl-L-arginine or nitro-L-arginine methyl ester, was also protective against vascular injury, suggesting that metabolic products of L-arginine participate in events leading to injury.
AuthorsA Seekamp, M S Mulligan, G O Till, P A Ward
JournalThe American journal of pathology (Am J Pathol) Vol. 142 Issue 4 Pg. 1217-26 (Apr 1993) ISSN: 0002-9440 [Print] United States
PMID8386444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Arginine
  • Peroxidase
Topics
  • Animals
  • Arginine (analogs & derivatives, metabolism)
  • Capillary Permeability
  • Complement Hemolytic Activity Assay
  • Hemorrhage (chemically induced)
  • Hindlimb (blood supply)
  • Ischemia (metabolism, pathology)
  • Lung (metabolism, pathology)
  • Male
  • Muscles (metabolism, pathology)
  • Neutrophils (metabolism)
  • Peroxidase (metabolism)
  • Rats
  • Rats, Inbred Strains
  • Reperfusion Injury (metabolism, pathology)
  • Time Factors

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