title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Biomarker Core Laboratory, Atlanta VA Medical Center, Decatur, GA, USA; Emory University School of Medicine, Atlanta, GA, USA. Electronic address: anh.le@va.gov.
authors.forename: Ngoc-Anh
authors.initials: NA
authors.lastname: Le
authors.forename: Monica
authors.initials: M
authors.lastname: Farkas-Epperson
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Sweeney
authors.forename: Peter W F
authors.initials: PW
authors.lastname: Wilson
authors.forename: W
authors.initials: W
authors.lastname: Virgil Brown
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003300:Copper / Q000737:chemistry; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000737:chemistry; D019518:Postprandial Period / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D003300:Copper; C006012:fenofibric acid; D010100:Oxygen; D011345:Fenofibrate
keywords: ABT-335; Fenofibric acid; Metabolic syndrome; Oxidative susceptibility; Postprandial lipemia