Protective effects of the new lazaroid "U-83836E" in splanchnic artery occlusion (SAO) shock

Free Radic Res. 1998 May;28(5):477-84. doi: 10.3109/10715769809066885.

Abstract

We studied the effects of the new antioxidant drug U-83836E during splanchnic artery occlusion (SAO) shock in the rat. Serum tumor necrosis factor (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure (MAP), survival rate and the responsiveness to acetylcholine of aortic rings were investigated. SAO shock produced a marked increase in serum TNF-alpha (241.4 +/- 18.2 U/ml vs Not Detectable in basal), reduced MAP (51.4 +/- 4 mmHg vs 85.1 +/- 5 mmHg), survival time (80 +/- 10 min vs > 240 min), WBC count (2.8 +/- 0.4 x 10(3)/mm3 cells vs 11.7 +/- 0.9 x 10(3)/mm3 cells) and blunted the responsiveness to ACh of aortic rings (60 +/- 3% tension vs 23 +/- 4% tension). The analogue of vitamin E, U-84836E, administered at onset of reperfusion, lowered serum TNF-alpha (38.4 +/- 6.5 U/ml; p < 0.001), improved MAP (67.5 +/- 3.8 mmHg; p < 0.001), WBC count (8.9 +/- 0.6 x 10(3)/mm3; p < 0.001), and survival time (235 +/- 15 min; p < 0.001), and restored the responsiveness to ACh of aortic rings (32 +/- 3.7% tension; p < 0.001). These preliminary data suggest that this new compound could be a promising drug in shock therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Antioxidants / pharmacology*
  • Arterial Occlusive Diseases / complications
  • Arterial Occlusive Diseases / drug therapy*
  • Blood Pressure / drug effects
  • Chromans / pharmacology*
  • Ischemia / prevention & control
  • Leukocyte Count / drug effects
  • Lipid Peroxidation / drug effects
  • Male
  • Piperazines / pharmacology*
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Shock / etiology
  • Shock / prevention & control*
  • Splanchnic Circulation / drug effects*
  • Survival Rate
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasodilator Agents / pharmacology

Substances

  • Antioxidants
  • Chromans
  • Piperazines
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • U 78517F
  • Acetylcholine