Impaired resistance to oxidation of low density lipoprotein in cystic fibrosis: Improvement during vitamin E supplementation

• Published in: Free radical biology & medicine 1995-12, Vol.19 (6), p.725-733
• Main Authors: Winklhofer-Roob, Brigitte M., Ziouzenkova, Ouliana, Puhl, Herbert, Ellemunter, Helmut, Greiner, Peter, Müller, Guido, Van't Hof, Martin A., Esterbauer, Hermann, Shmerling, David H.
• Format: Article
• Language: English
• Subjects: Adult; Antioxidants - administration & dosage; Arachidonic acid; Copper - pharmacology; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - metabolism; Fatty Acids - blood; Free radicals; Humans; Linoleic acid; Lipid Peroxidation - drug effects; Lipoproteins, LDL - metabolism; Low density lipoprotein; Oxidation resistance; Oxidation-Reduction; Vitamin E - administration & dosage; Vitamin E - blood; Vitamin E - therapeutic use; Vitamin E Deficiency - complications; Vitamin E Deficiency - drug therapy; α-Tocopherol
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/0891-5849(95)00063-4

Antioxidants such as vitamin E protect unsaturated fatty acids of LDL against oxidation. In the ex vivo model used, LDL was exposed to Cu 2+ ions, a potent prooxidant capable of initiating the oxidation of LDL. The lag time, indicating the delay of conjugated diene formation in LDL due to antioxidant protection, was measured in 54 cystic fibrosis (CF) patients with plasma α-tocopherol levels below (Group A, n = 30) or above (Group B, n = 24) 15.9 μmol/ L (mean - 2 SD of Swiss population). Patients were reevaluated after 2 months on 400 IU/d of oral RRR-α-tocopherol. In group A, α-tocopherol concentrations in LDL increased significantly from 3.2 ± 1.6 mol/mol LDL to 8.2 ± 2.8 mol/mol ( P < 0.001) and lag times increased from 79 ± 33, min to 126 ± 48 min ( P < 0.001), whereas in the vitamin E sufficient group B no further increase neither in LDL α-tocopherol concentrations or in lag times was observed. LDL oleic acid concentrations were higher, and linoleic acid concentrations were lower in patients than in controls. After efficient vitamin E supplementation, lag times were positively related to LDL α-tocopherol ( P < 0.01) and negatively to LDL linoleic and arachidonic acid content ( P < 0.001). The maximum rate of oxidation correlated positively with linoleic and arachidonic acid concentrations, as did the maximum conjugated diene absorbance. These results indicate that LDL resistance to oxidation is impaired in vitamin E deficient CF patients but can be normalized within 2 months when α-tocopherol is given in sufficient amounts. Linoleic and arachidonic acid content exhibit a major influence on the LDL resistance to oxidation.