Peroxidative Hemolysis of Red Blood Cells from Patients with Abetalipoproteinemia (Acanthocytosis)*

Abstract

The effect of peroxidative stress on tissue was studied by exposure of red blood cells (RBC) from patients with abetalipoproteinemia to minute amounts of H₂O₂in vitro. Red blood cells from untreated patients showed a marked sensitivity to H₂O₂, as evidenced by hemolysis and lipid peroxidation (peroxidative hemolysis). The appearance of lipid peroxidation products in sensitive cells after exposure to H₂O₂ was indicated by 1) increases in the 2-thiobarbituric acid (TBA) reaction of trichloroacetic acid extracts, 2) increases in ultraviolet light absorbency of lipid extracts, and 3) decreases in polyunsaturated fatty acids. These changes were accompanied by a decrease in phosphatidyl ethanolamine and phosphatidyl serine in the RBC lipid extract. Similar lipid changes on exposure to H₂O₂ were observed in the RBC from vitamin E-deficient rats. Treatment of the patients with d-α-tocopherol polyethylene glycol succinate by mouth, or addition of dl-α-tocopherol to the incubation medium protected the RBC from peroxidative hemolysis. Tocopherol appears to provide a primary biologic defense against peroxidative hemolysis. The presence of nitrite or carbon monoxide, which produced methemoglobin and carboxyhemoglobin, respectively, inhibited peroxidative changes, suggesting a catalytic role for oxy- or deoxyhemoglobin. Substances that prevented lipid peroxidation also prevented hemolysis; in addition, lipid peroxidation appeared to precede hemolysis. These observations suggested that hemolysis was a consequence of lipid peroxidation.