[Non-antioxidative mechanism of cytochrome P-450 stabilization by alpha-tocopherol: the effectiveness in avitaminosis...

The efficiency of alpha-tocopherol as a 7-etoxycumarine deethylase protector in rat liver microsomes damaged by phospholipase A2 at various levels of vitamin E was studied. No selective damage of cytochrome P-450 isoforms possessing a catalytic activity towards 7-etoxycumarine under vitamin E deficiency was observed. Phospholipase A2 decreased the deethylase activity of cytochrome P-450, the efficiency of the damaging action being dependent on vitamin E content in the liver. Exogenous alpha-tocopherol exerts an antiphospholipase effect and protects 7-etoxycumarine deethylase; the protective action is inversely proportional to vitamin E level in the liver. Under normal conditions the damaging effect of phospholipase A2 on cytochrome P-450 is mainly provided for by lysophospholipids, while under vitamin E deficiency both lysophospholipids and free fatty acids exert a damaging action. A possible mechanism of the stabilizing effect of alpha-tocopherol may consist in the interaction of the chromanol nucleus in the vitamin E molecyule both with lysophospholipids and with free fatty acids.