Standard treatment of alpha-tocopherol in alagille patients with severe cholestasis is insufficient

Alpha-tocopherol (alpha -T) is the most effective lipid-soluble antioxidant present in cells. We investigated the efficacy of alpha -T supplements for preventing lipid peroxidation in patients with Alagille syndrome, accordin g to the severity of cholestasis. Patients were assigned to two groups on t he basis of plasma bilirubin concentration (group I, bilirubin <100 <mu>M: group II, bilirubin >100 muM) alpha -T concentrations were determined in pl asma, in isolated lipoproteins. and in red blood cell membranes. In both gr oups of patients, alpha -T concentrations in plasma were similar to those i n control subjects, but the distribution of alpha -T in lipoproteins was af fected by the abnormal lipoprotein pattern in these patients. The efficacy of alpha -T was estimated by determining the amount of hydroperoxide produc ed from phosphatidylcholine and phosphatidylethanolamine (PE) molecular spe cies owing to oxidative stress induced by lipoxygenase treatment. The conce ntrations of phosphatidylcholine molecular species and its corresponding hy droperoxides were significantly higher in both groups of patients. In group I, alpha -T and PE molecular species concentrations were similar to those in control subjects, but PE hydroperoxide concentrations were higher than t hose in the control subjects. In group II, alpha -T concentration was signi ficantly lower and the concentrations of some PE molecular species and all PE hydroperoxides were lower than those in the control subjects. In conclus ion, erythrocyte membrane alpha -T concentration was significantly lower on ly in patients with severe jaundice. despite alpha -T supplementation, rais ing the question as to whether the usual treatment was appropriate in this group.