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

Abstract
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.
AuthorsA Davit-Spraul, C Cosson, M Couturier, M Hadchouel, A Legrand, F Lemonnier, P Therond
JournalPediatric research (Pediatr Res) Vol. 49 Issue 2 Pg. 232-6 (Feb 2001) ISSN: 0031-3998 [Print] United States
PMID11158519 (Publication Type: Journal Article)
Chemical References
  • Phospholipids
  • Vitamin E
  • Cholesterol
Topics
  • Adolescent
  • Alagille Syndrome (blood, complications, drug therapy)
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cholestasis (blood, complications, drug therapy)
  • Cholesterol (blood)
  • Humans
  • Infant
  • Phospholipids (blood)
  • Vitamin E (blood, therapeutic use)

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