Clofibric Acid

Clofibric acid increases CYP4A6 gene expression in RK13 cells transfected with PPAR-G with EC50 of 80 μM. ^[1] Clofibric acid (1 mM) treatment for 4 days induces 500-fold increase of P450 4Al RNA and 280-fold increase of acyl-CoA oxidase and P450 2Bl RNA in hepatocytes, relative to control cultures. ^[2] Clofibric acid (250 μM) induces up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent. Clofibric acid treatment is able to cause up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. Clofibric acid also up-regulates genes expression of the cytosolic, microsomal, and mitochondrial pathways involved in fatty acid transport and metabolism in both rodent and human hepatocyte cultures, and increases genes level of the peroxisomal pathway of lipid metabolism in rodents. An up-regulation of hepatocyte nuclear factor 1α (HNF 1α) by Clofibric acid is observed in human hepatocyte cultures. ^[3] Clofibric acid also dose-dependently inhibits cell proliferation of cultured OVCAR-3 and DISS cells derived from human ovarian cancer. Clofibric acid treatment increases the expression of carbonyl reductase, which promotes the conversion of prostaglandin E2 (PGE2) to PGF 2α. ^[4]

Clofibric acid (50 mg/kg) treatment 4 days by gavage induces both P450 4A and BFB expression in zones 3 and 2 of the liver acinus in rats. 300 mg/kg of Clofibric acid causes a strong staining of both proteins throughout the liver acinus. ^[2] Clofibric acid (9,000 ppm) treatment in diet significantly suppresses the growth of OVCAR-3 tumors xenotransplanted s.c. (46%) and significantly prolongs the survival of mice with malignant ascites derived from DISS cells as compared with control. Clofibric acid treatment increases the expression of carbonyl reductase in vivo. Clofibric acid treatment decreases PGE2 level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3–tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis are in solid OVCAR-3 tumors treated by Clofibric acid. ^[4]