ANTIOXIDANT ACTIVITY OF EBSELEN AND RELATED SELENOORGANIC COMPOUNDS IN MICROSOMAL LIPID-PEROXIDATION

Ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)one, and its derivatives were compared for their ability to protect microsomal membranes against iron/ADP/ascorbate-induced lipid peroxidation, measured as low-level chemiluminescence and accumulation of thiobarbituric acid-reactive substances (TBARS). The concentrations of the compounds required to double the lag time of the control with no added antioxidants were 0.13μM for ebselen, 0.5μM for the N-pyridyl analog, 0.3-0.7 μM for the selenylsulfides, about 1.0 μM for the selenoxide derivative and 2.0 μM for the sulfur analog of ebselen. The open-chain seleno- and thioether derivatives, on the other hand, exhibited comparatively low abilities to protect the membrane, the lag doubling concentrations for these compounds being 100-1,000 fold higher than that for ebselen. The rate of loss of αtocopherol in the microsomal membrane during peroxidation was significantly diminished in the presence of 0.1-0.5μM ebselen, while the glutathione adduct of ebselen was equally effective in protecting the loss of αtocopherol. The sulphur analogue and, the benzylated and methylated derivatives of ebselen did not afford protection. Ebselen was without effect in microsomes from vitamin E-deficient rats up to 20μM, indicative of the dependence of its protective ability upon αtocopherol. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.