RABBIT BRAIN ENDOPLASMIC-RETICULUM MEMBRANES AS TARGET FOR FREE-RADICALS - CHANGES IN CA2-TRANSPORT AND PROTECTION BY STOBADINE()

Incubation of rabbit brain endoplasmic reticulum membranes with either ferrous sulfate/EDTA or ferrous sulfate/EDTA and hydrogen peroxide le d to the loss of efficiency of membranes to sequester Ca2(+), which di d not correlate with changes in conjugated diene formation. The produc tion of practically non-detectable amount of conjugated dines that occ urs during the period of incubation of microsomes with lipid peroxidat ion initiators represents lipid peroxidation that is enough to produce changes in membrane permeability towards Ca2(+). Addition of stobadin e was able to prevent Ca2(+) transport damage in a dose-dependent mann er and drug concentrations higher than 200 mu M were able in our model system to confer the defense against free radical and heavy metal ini tiated lipid peroxidation. The EC(50) values for microsomes treated wi th Fe2+ and Fe2+/H2O2, were 12 mu M and 25 mu M, respectively. In our model system stobadine seems to be at least as effective as butylated hydroxytoluene, which is considered to be a good chain-breaking antiox idant. In contrast to stobadine alpha-tocopherole acetate was less pot ent; the effect of 1 mM alpha-tocopherole acetate being comparable to the effect of 20 mu M stobadine.