title: Pleiotropic effects of fenofibrate therapy on rats with hypertriglycemia.
abstract: BACKGROUND
  Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia.
  
  
  METHODS
  Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks. At baseline, 4 weeks of fructose administration and 2 weeks of fenofibrate therapy, parameters of interest were evaluated and compared.
  
  
  RESULTS
  At baseline, no significant differences of parameter were observed between groups. After 4 weeks of fructose prescription, triglyceride level increased in company with high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) decreased. C-reactive protein (CRP) and malondialdehyde (MDA) levels were also elevated. Endothelial function was impaired as reflected by reduced nitric oxide (NO) production and elevated serum asymmetric dimethylarginine (ADMA) level. All these changes were significant as compared to the control group (P<0.05), suggesting that short-term of triglyceride elevation could potently initiate atherosclerosis. With 2 weeks of fenofibrate therapy, in comparison to un-treated group, triglyceride level was significantly reduced in parallel with HDL-C and ApoA1 elevation. Inflammation and oxidation were also profoundly ameliorated as reflected by CRP and MDA reduction. Notably, NO production was enhanced in company with serum ADMA level decrease. Overall, these improvements manifested in a dose-dependent manner, which was supported by multivariate regression analysis showing that after adjusted to other variables, the dose of fenofibrate therapy remained significantly associated with NO production and serum ADMA level, with OR of 1.042 (high-dose versus low-dose, 95% CI 1.028-1.055, P<0.05).
  
  
  CONCLUSIONS
  Fenofibrate therapy not only could reduce triglyceride level but also confer pleiotropic effects in terms of endothelium-protection and amelioration of inflammation and oxidation in a dose-dependent manner.
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, 200092, China. wowocncn@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, 200092, China. doctorxieyuan@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, 200092, China. mdjiangjingfa@163.com.
authors.forename: Jinfa
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, 200092, China. mdwangyiping@163.com.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, 200092, China. xiaolinxu123@163.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, 200092, China. cardiologyzcm@163.com.
authors.forename: Cuimei
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji University, Shanghai, 200092, China. ffhuang18@163.com.
authors.forename: Feifei
authors.initials: F
authors.lastname: Huang
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D002316:Cardiotonic Agents; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D009569:Nitric Oxide; D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine; D011345:Fenofibrate