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.