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, according to the severity of
cholestasis. Patients were assigned to two groups on the basis of plasma
bilirubin concentration (group I,
bilirubin <100 microM; group II,
bilirubin >100 microM). alpha-T concentrations were determined in plasma, in isolated
lipoproteins, and in red blood cell membranes. In both groups of patients, alpha-T concentrations in plasma were similar to those in control subjects, but the distribution of alpha-T in
lipoproteins was affected by the abnormal
lipoprotein pattern in these patients. The efficacy of alpha-T was estimated by determining the amount of
hydroperoxide produced from
phosphatidylcholine and
phosphatidylethanolamine (PE) molecular species owing to oxidative stress induced by
lipoxygenase treatment. The concentrations of
phosphatidylcholine molecular species and its corresponding hydroperoxides 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 those in the control subjects. In group II, alpha-T concentration was significantly lower and the concentrations of some PE molecular species and all PE hydroperoxides were lower than those in the control subjects. In conclusion, erythrocyte membrane alpha-T concentration was significantly lower only in patients with severe
jaundice, despite alpha-T supplementation, raising the question as to whether the usual treatment was appropriate in this group.