High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia.
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.
Pan
Si-Yuan
SY
Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100029, China. siyuan-pan@163.com
Yang
Rong
R
Han
Yi-Fan
YF
Dong
Hang
H
Feng
Xu-Dong
XD
Li
Na
N
Geng
Wei
W
Ko
Kam-Ming
KM
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
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001713:Biphenyl Compounds; D000960:Hypolipidemic Agents; D014280:Triglycerides; C465548:bifendate; D002784:Cholesterol; D011345:Fenofibrate