75. High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia

PAN, Si-yuan; YANG, Rong¹; HAN, Yi-fan²; DONG, Hang¹; FENG, Xu-dong¹; LI, Na¹; GENG, Wei¹; KO, Kam-ming²

Aim: 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. Conclusion: The findings suggest that bifendate treatment at high oral doses can cause an acute elevation in serum and hepatic TG levels.

Keywords: bifendate; fenofibrate; inositol nicotinate; triglycerides; total cholesterol; acute hypertriglyceridemia