Normal oxidative stress and enhanced lipoprotein resistance to in vitro oxidation in hypertriglyceridemia Effects of bezafibrate therapy
article
Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F2-isoprostanes (8-isoprostaglandin F(2α) and 2,3-dinor-5,6-dihydro-8-isoprostaglandin F(2α)) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG and 20 matched control subjects. In addition, the effects of 6 weeks of bezafibrate therapy were assessed in a double-blind, placebo-controlled, crossover trial. Urinary levels of F2-isoprostanes were similar in the HTG and normolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F(2α) (762 ± 313 versus 552 ± 245 ng/24 h for bezafibrate and placebo therapy, respectively; P = 0.03), whereas 2,3-dinor-5,6-dihydro-8-isoprostaglandin F(2α) levels tended to be increased (1714 ± 761 versus 1475 ± 606 ng/24 h for bezafibrate and placebo therapy, respectively; P = 0.11). VLDLs and LDLs were more resistant to copper-induced oxidation in patients with HTG than in control subjects. Bezafibrate reversed the oxidation resistance to the normal range. In conclusion, these results indicate the following: (1) HTG is associated with normal in vivo oxidative stress and enhanced ex vivo resistance of lipoproteins to oxidation. (2) Bezafibrate reduces the resistance of lipoproteins to copper-induced oxidation and enhances oxidative stress in HTG patients. Chemicals / CAS 8 isoprostaglandin F2 alpha, 27415-26-5; bezafibrate, 41859-67-0; cholesterol, 57-88-5; copper, 15158-11-9, 7440-50-8.
Topics
BezafibrateF2-isoprostanesHypertriglyceridemiaLDL oxidationVLDL oxidation8 isoprostaglandin F2 alphabezafibratecholesterolcopperisoprostanelipoproteinlow density lipoproteinvery low density lipoproteinadultcholesterol blood levelclinical articleclinical trialcontrolled clinical trialcontrolled studycrossover proceduredouble blind proceduredrug effectfatty acid desaturationfemalehumanhyperlipidemiahypertriglyceridemialipid oxidationmaleoxidative stresspriority journalrandomized controlled trialurine level
TNO Identifier
953523
ISSN
10795642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 20(11), pp. 2434-2440.
Pages
2434-2440
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