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

2-t-Butyl-4-methoxy-phenol (BHA), 3,5-di-t-butyl-hydroxyanisole, (DTBHA), 2 ,6-diisopropylphenol (propofol), alpha -tocopherol (X-TOC) and two newly sy nthesised 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-but yl)-phenyl-beta -D-glucopyranose, (beta -GLU), were tested for their capabi lity to protect the intrinsic nerves of guinea-pig urinary, bladder from da mage due to anoxia-glucopenia and re-exposure to glucose and O-2. Guinea-pig detrusor strips were mounted for tension recording in small orga n baths, superfused with warmed Krebs solution and the nerves, stimulated e lectrically either under control or ischaemia-like (anoxia-glucopenia), and reperfusion-like conditions (normal medium re-superfusion). The Ca2+ antag onist activity of the compounds was. assessed by their effect on the contra ction 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 lin oleic acid oxidation. All the compounds, except beta -GLU and alpha -TOC, i nhibited in a concentration-dependent manner K+-induced contractions of det rusor muscles, the inhibition being inversely related to the Ca2+ concentra tion of the perfusion solution; moreover, they exhibited a marked antiperox idant activity with pIC(50) 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-glucop enia 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 ac tivity, but not to their Ca2+ antagonist activity.