Effect of ciprofibrate on fibrinogen synthesis in vitro on hepatoma cells and in vivo in genetically obese Zucker rats

In this study, we have shown that oncostatin M and interleukin-6 induce a d ose- and time-dependent increase in fibrinogen levels in the conditioned me dium of human hepatoma cells (HepG2). When HepG2 cells were treated simulta neously with oncostatin M or interleukin-6 and ciprofibrate (100 nmol/l), t he production of fibrinogen in the conditioned media was strongly affected and a significant decrease in the mRNA levels of the fibrinogen beta chain was observed. Oncostatin-M- and interleukin-6-induced fibrinogen release wa s inhibited in a dose-dependent manner by ciprofibrate and, to lesser exten t, by bezafibrate, fenofibric acid and clofibric acid. In vivo, increased p lasma and platelet levels of fibrinogen were observed in genetically obese Zucker rats (fa/fa) compared with Zucker lean (fa/-) rats. In these rats, a 14-day oral treatment with ciprofibrate (10 mg/kg, per. os.) induced a sta tistically significant decrease (P>0.05) in plasma concentrations of total cholesterol and triglyceride but also in plasma and platelet levels of fibr inogen. In order to determine the consequences of such an effect on fibrino gen, the ability of ciprofibrate to affect venous stasis was determined in a stasis-induced venous thrombosis model in Zucker rats. Under low thrombog enic challenge, ciprofibrate significantly inhibited thrombus formation (67 +/- 12%, P > 0.05), demonstrating for the first time that a potent hypolip emic compound exhibits an antithrombotic effect. Blood Coag Fibrinol 10:239 -244 (C) 1999 Lippincott Williams & Wilkins.