Degradation of Membrane Phospholipids and Thiols in Peroxide Hemolysis: Studies in Vitamin E Deficiency

To understand more clearly the hemolytic anemia associated with administration of certain oxidant drugs, the mechanism by which H₂O₂ causes hemolysis in rat red cells, deficient in vitamin E was investigated. It was demonstrated that the locus of attack by H₂O₂ was the red cell membrane, in which one phospholipid, i.e., phosphatidyl ethanolamine, was specifically destroyed prior to the onset of hemolysis. No perturbation of intracellular components or metabolism was noted during peroxidative hemolysis. E-deficient red cells incorporated ¹⁴C-labelled fatty acids into this phosphatide at nearly twice the rate that in E-supplemented cells, reflecting the continual tendency of phosphatidyl ethanolamine to be destroyed. Young red cells were especially active in this regard and concomitantly were less vulnerable to damage by H₂O₂ both in vitro and when circulating in rats exposed to hyperbaric oxygenation. If, however, replacement of fatty acids in phosphatidyl ethanolamine was prevented by inhibition of metabolism or if fatty acids were enzymatically removed by a phospholipase-A, H₂O₂ hemolysis was potentiated. Hemolysis was also associated with, and potentiated by, loss of membrane sulfhydryl activity. It is suggested that hemolytic anemia may occur in patients with vitamin E deficiency (i.e., with steatorrhea) if oxidant drugs capable of generating H₂O₂ and oxidizing membrane thiols are administered. Two such cases are under investigation.