Kinetics of NADPH-dependent lipid peroxidation and a possible initiation-preventing antioxidant effect of microsomal...

The initial part of NADPH-driven lipid peroxidation was investigated in liver microsomes. Without the addition of any antioxidant or pretreatment of animals with vitamin E, a delay was observed in the malondialdehyde and lipid hydroperoxide formation, but not in oxygen consumption. The duration of lag and the effect of ADP-Fe2+ on it showed differences in rat, mouse, chicken and rabbit microsomes. As it was not caused by cytoplasmic contaminations, this lag was an indication of the antioxidant capacity of microsomes, possibly due to the oxidation of their (+)-alpha-tocopherol content. The length of lag was dependent on the NADPH-cytochrome-P-450 reductase activities and the concentration of Fe-ion complexes. The results presented here suggest that (+)-alpha-tocopherol acted during the lag as an initiation-preventing rather than a chain-breaking antioxidant in rat liver microsomes. The lag may explain the known differences found in the inducibility and intensity of lipid peroxidation of microsomes from various species, and provides means to elucidate the molecular mechanism of vitamin E action against free radicals formed in a membrane of biological origin.