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

摘要

2-t-Butyl-4-methoxyphenol (BHA), 3,5-di-t-butyl-hydroxyanisole (DTBHA), 2,6-diisopropylphenol (propofol), α-tocopherol (α-TOC) and two newly synthesised analogues of BHA, namely 1-O-(4-hydroxy-3-t-butyl)phenyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (β-TAG) and 1-O-(4-hydroxy-3-t-butyl)phenyl-β-D-glucopyranose (β-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.nGuinea-pig detrusor strips were mounted for tension recordingnin small organ baths, superfused with warmed Krebsnsolution and the nerves stimulated electrically either underncontrol or ischaemia-like (anoxia-glucopenia) and reperfusion-nlike conditions (normal medium re-superfusion). ThenCa2+ antagonist activity of the compounds was assessednby their effect on the contraction of detrusor strips inducednby 60 mM K+ Krebs solution in the presence of eithern0.5 mM or 5 mM Ca2+. The antioxidant activity wasnillustrated by the ability of the compounds to scavengenperoxyl radicals generated by linoleic acid oxidation. Allnthe compounds, except β-GLU and α-TOC, inhibited in anconcentration-dependent manner K+-induced contractionsnof detrusor muscles, the inhibition being inversely relatednto the Ca2+ concentration of the perfusion solution; moreover,nthey exhibited a marked antiperoxidant activity withnpIC50 values decreasing in the order: DTBHA > α-TOC >nBHA > β-TAG > propofol > β-GLU.nα-TOC, BHA, DTBHA and β-TAG improved significantlynthe response of the strips to electrical field stimulationneither during the anoxia-glucopenia phase or thereafternwhen recovering during reperfusion, as compared tonuntreated tissues. The neuroprotection afforded by thenphenol derivatives as well as by α-TOC was positivelyncorrelated to their antioxidant activity, but not to theirnCa2+ antagonist activity.