Protective Effects of the New Lazaroid “U-83836E” in Splanchnic Artery Occlusion (SAO) Shock

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-α), 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-α (241.4 ± 18.2 U/ml vs Not Detectable in basal), reduced MAP (51.4 ± 4mmHg vs 85.1± 5mmHg), survival time (80±10min vs >240min), WBC count (2.8 ± 0.4 × 10³/mm³ cells vs 11.7±0.9 × 10³/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-α (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 × 10³/mm³; p < 0.001), and survival time (235±15min; 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.

Key Words:

• Antioxidants
• free radicals
• lipid peroxidation
• vitamin E
• splanchnic artery occlusion shock