Urinary trypsin inhibitor suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats

Neurol Res. 2010 Nov;32(9):925-32. doi: 10.1179/016164110X12645013515133. Epub 2010 Mar 10.


Objectives: To investigate the effects of ulinastatin, a urinary trypsin inhibitor (UTI), on jugular venous superoxide radical (O₂⁻·) generation, oxidative stress, early inflammation, and endothelial activation in forebrain ischemia/reperfusion (FBI/R) rats.

Methods: Fourteen Wistar rats were allocated to a control group (n = 7) and a UTI group (n = 7). Throughout the experiments, O₂⁻· in the jugular vein was measured by the produced current using a novel electrochemical O₂⁻· sensor. Forebrain ischemia was induced by occlusion of the bilateral common caroti darteries with hemorrhagic hypotension for 20 min, followed by reperfusion. In the UTI group, UTI (5 U/g) was administered intravenously immediately after reperfusion. At 60 min after reperfusion, plasma and brain were harvested, and malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule-1 (ICAM-1) were measured.

Results: O₂⁻· current increased gradually during forebrain ischemia in both groups. The current increased markedly in the control group immediately after reperfusion but was significantly attenuated in the UTI group after reperfusion. Brain and plasma malondialdehyde, HMGB1, and ICAM-1 were significantly attenuated in the UTI group compared with those in the control group, except for brain HMGB1, which was associated with the amount of O₂⁻· generated during FBI/R.

Discussion: UTI suppressed jugular venous O₂⁻· generation, oxidative stress, early inflammation, and endothelial activation in FBI/R rats. Therefore, UTI might be a useful agent for the therapy of the cerebral ischemia/reperfusion pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Gas Analysis / methods
  • Brain Ischemia* / blood
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / pathology
  • Disease Models, Animal
  • Endothelium / drug effects
  • Endothelium / injuries
  • Glycoproteins / drug effects
  • Glycoproteins / pharmacology*
  • Inflammation / drug therapy
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects*
  • Prosencephalon / pathology
  • Rats
  • Rats, Wistar
  • Reperfusion
  • Superoxides / blood*
  • Trypsin Inhibitors / pharmacology*


  • Glycoproteins
  • Trypsin Inhibitors
  • Superoxides
  • Intercellular Adhesion Molecule-1
  • Malondialdehyde
  • urinastatin