Normal oxidative stress and enhanced lipoprotein resistance to in vitro oxidation in hypertriglyceridemia - Effects of bezafibrate therapy

Although there is evidence that hyperlipidemia and predominance of small de nse low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) h as not been studied in detail. Therefore, we studied urinary levels of F-2- isoprostanes (8-isoprostaglandin F-2 alpha and 2,3-diner-5,6-dihydro-8-isop rostaglandin F-2 alpha) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG a nd 20 matched control subjects. In addition, the effects of 6 weeks of beza fibrate therapy were assessed in a double-blind, placebo-controlled, crosso ver trial. Urinary levels of F-2-isoprostanes were similar in the HTG and n ormolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F -2 alpha (762+/-313 versus 552+/-245 ng/24 h for bezafibrate and placebo th erapy, respectively; P=0.03), whereas 2,3-dinor-5,6-dihydro-8-isoprostaglan din F-2 alpha levels tended to be increased (1714+/-761 versus 1475+/-606 n g/24h for bezafibrate: and placebo therapy, respectively; P=0.11). VLDLs an d 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 exvivo resistance of lipoproteins to oxidation. (2) Bezafibrate reduces the resis tance of lipoproteins to copper-induced oxidation and enhances oxidative st ress in HTG patients.