Neuroprotection afforded by some hindered phenols and alpha-tocopherol in guinea-pig detrusor strips subjected to anoxia-glucopenia and reperfusion-like conditions

Naunyn Schmiedebergs Arch Pharmacol. 2001 Nov;364(5):462-71. doi: 10.1007/s002100100471.

Abstract

2-t-butyl-4-methoxyphenol (BHA), 3,5-di-t-butyl-hydroxyanisole (DTBHA), 2,6-diisopropylphenol (propofol), alpha-tocopherol (alpha-TOC) and two newly synthesised analogues of BHA, namely 1-O-(4-hydroxy-3-t-butyl)phenyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranose (beta-TAG) and 1-O-(4-hydroxy-3-t-butyl)phenyl-beta-D-glucopyranose (beta-GLU), were tested for their capability to protect the intrinsic nerves of guinea-pig urinary bladder from damage due to anoxia-glucopenia and re-exposure to glucose and O2. Guinea-pig detrusor strips were mounted for tension recording in small organ baths, superfused with warmed Krebs solution and the nerves stimulated electrically either under control or ischaemia-like (anoxia-glucopenia) and reperfusion-like conditions (normal medium re-superfusion). The Ca2+ antagonist activity of the compounds was assessed by their effect on the contraction of detrusor strips induced by 60 mM K+ Krebs solution in the presence of either 0.5 mM or 5 mM Ca2+. The antioxidant activity was illustrated by the ability of the compounds to scavenge peroxyl radicals generated by linoleic acid oxidation. All the compounds, except beta-GLU and alpha-TOC, inhibited in a concentration-dependent manner K+-induced contractions of detrusor muscles, the inhibition being inversely related to the Ca2+ concentration of the perfusion solution; moreover, they exhibited a marked antiperoxidant activity with pIC50 values decreasing in the order: DTBHA > alpha-TOC > BHA > beta-TAG > propofol > beta-GLU. alpha-TOC, BHA, DTBHA and beta-TAG improved significantly the response of the strips to electrical field stimulation either during the anoxia-glucopenia phase or thereafter when recovering during reperfusion, as compared to untreated tissues. The neuroprotection afforded by the phenol derivatives as well as by alpha-TOC was positively correlated to their antioxidant activity, but not to their Ca2+ antagonist activity.

MeSH terms

  • Analysis of Variance
  • Animals
  • Antioxidants / therapeutic use*
  • Female
  • Guinea Pigs
  • Hypoxia
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Neuroprotective Agents / therapeutic use*
  • Phenols / therapeutic use*
  • Reperfusion Injury / prevention & control*
  • Structure-Activity Relationship
  • alpha-Tocopherol / therapeutic use*

Substances

  • Antioxidants
  • Neuroprotective Agents
  • Phenols
  • alpha-Tocopherol