title: High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia.
abstract: OBJECTIVE
  To investigate the effects of bifendate on serum and hepatic lipids level in rabbits and mice.
  
  
  METHODS
  Animals were administered bifendate [powdered pill suspended in 0.5% sodium carboxymethylcellulose (CMC)] at increasing doses (0.25-1 g/kg, ig). Blood lipid and apolipoprotein levels were measured using commercially available assay kits.
  
  
  RESULTS
  The treatment of rabbits with a single dose of bifendate (0.3 g/kg) caused a time-dependent and biphasic change in serum triglyceride (TG) levels, with the value reaching a maximum (3-fold increase compared to the baseline value) between 24 and 36 h post-dosing. When mice were orally treated with bifendate (0.25-1 g/kg), serum TG levels increased by 39%-76% and 14%-39% at 24 and 48 h post-dosing, respectively. When given at daily doses of 0.25 and 1 g/kg for 4 d, bifendate increased serum TG levels (56%-79%), with concomitant elevations in apolipoprotein A-I and apolipoprotein B levels at 24 h after the last dosing. TG levels were also increased (11%-43%) in liver samples of mice receiving single or multiple doses of bifendate. However, bifendate treatment caused slight reductions in serum and hepatic total cholesterol levels (9%-13%). The hypertriglyceridemia induced by bifendate was ameliorated by fenofibrate but not inositol nicotinate treatment in mice.
  
  
  CONCLUSIONS
  The findings suggest that bifendate treatment at high oral doses can cause an acute elevation in serum and hepatic TG levels.
authors.affiliation: Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100029, China. siyuan-pan@163.com
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Pan
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Han
authors.forename: Hang
authors.initials: H
authors.lastname: Dong
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Feng
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Geng
authors.forename: Kam-Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000494:pharmacology; D015228:Hypertriglyceridemia / Q000097:blood / Q000139:chemically induced*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011817:Rabbits; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001713:Biphenyl Compounds; D000960:Hypolipidemic Agents; D014280:Triglycerides; C465548:bifendate; D002784:Cholesterol; D011345:Fenofibrate