Effect of ABT-335 (fenofibric acid) on meal-induced oxidative stress in patients with metabolic syndrome.

Abstract

OBJECTIVE:

Examine the effect of ABT-335 (fenofibric acid) on postprandial lipemia and susceptibility of plasma lipoproteins to Cu(++)-mediated oxidation in patients with metabolic syndrome.

METHODS AND RESULTS:

This is a randomized double-blind, placebo-controlled study with cross-over and includes a 4-week wash-out period between the two treatment periods. At the end of each 8-week treatment period, subjects were challenged with a standardized mixed meal followed by blood collection over the ensuing 6 h. Plasma lipoproteins were isolated by a combination of ultracentrifugation and FPLC for the continuous monitoring of conjugated dienes formation as an assessment of oxidative susceptibility. Fasting plasma TG was reduced by 20% (p < 0.0002) and there was a modest reduction in hsCRP (6.1%, p < 0.06). There was no change in either HDLc or LDLc in these subjects. Postprandial lipemia was reduced with ABT-335 as demonstrated by a 28.5% reduction (p < 0.0005) in incremental area under the curve for TG during the 6-h period after the meal challenge. Lag times for both fasting LDL (+16%) and postprandial LDL (+28%) were increased with the ABT-335 therapy, suggestive of reduced oxidative susceptibility. Co-incubation with autologous HDL did not reduced LDL oxidative susceptibility in these patients.

CONCLUSION:

ABT-335 therapy reduced fasting and postprandial triglycerides in patients with metabolic syndrome. Autologous HDL may be dysfunctional in these patients as co-incubation with HDL failed to reduce oxidative susceptibility of LDL. During ABT-335 therapy, LDL was less susceptible to Cu(++)-mediated oxidative modification, in spite of the lack of changes in LDLc levels.

• Authors: Ngoc-Anh Le, Monica Farkas-Epperson, Mary Ellen Sweeney, Peter W F Wilson, W Virgil Brown
• Journal: Atherosclerosis (Atherosclerosis) Vol. 231 Issue 2 Pg. 268-73 (Dec 2013) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 24267238 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Ireland Ltd.

Chemical References

• Anticholesteremic Agents
• Antioxidants
• Cholesterol, HDL
• Cholesterol, LDL
• Triglycerides
• Copper
• fenofibric acid
• Oxygen
• Fenofibrate

Topics

• Adult
• Aged
• Anticholesteremic Agents (therapeutic use)
• Antioxidants (chemistry)
• Cholesterol, HDL (blood)
• Cholesterol, LDL (blood)
• Copper (chemistry)
• Cross-Over Studies
• Double-Blind Method
• Female
• Fenofibrate (analogs & derivatives, therapeutic use)
• Humans
• Hyperlipidemias (blood)
• Male
• Metabolic Syndrome (drug therapy)
• Middle Aged
• Oxidative Stress (drug effects)
• Oxygen (chemistry)
• Postprandial Period (drug effects)
• Triglycerides (blood)