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

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.
AuthorsF Pessina, R Kalfin, L Esposito, F Fusi, M Valoti, F Ponticelli, G Sgaragli
JournalNaunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 364 Issue 5 Pg. 462-71 (Nov 2001) ISSN: 0028-1298 [Print] Germany
PMID11692230 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Neuroprotective Agents
  • Phenols
  • alpha-Tocopherol
Topics
  • 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)

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