Several hypolipidemic drugs, plasticizers and other chemicals induce peroxisome proliferation and hepatic tumors in rodents, but the mechanism by which they induce tumors is not fully understood. Their carcinogenic activity may be related to alterations in gene expression, such as induction of peroxisomal β-oxidation enzymes or of the cytochrome P450 4A family. These enzymes metabolize lipids, including eicosanoids and their precursor fatty acids. Because eicosanoids likely play a role in the carcinogenic process, alterations in their concentration by xenobiotics may be important in their carcinogenic or promoting activities. In this study we used isolated hepatocytes to study if peroxisome proliferators alter the metabolism of prostaglandins (PG) and thromboxanes (Tx). Isolated rat hepatocytes were cultured for 4 days with 2 concentrations of ciprofibrate (CIP): 100 and 400 μM. Fatty acyl CoA oxidase activities of the 100 and 400 μM CIP treatment groups at the end of the experiment were increased 5.3 and 9.6 times, respectively. TxB2 and PGF2α concentrations in cultures treated with CIP were significantly lower than the control at days 3 and 4, whereas a lower concentration of PGE2 was seen at day 4 only. These studies show that PG and Tx concentrations in cultured hepatocytes are lowered by the peroxisome proliferator CIP.
|Number of pages||7|
|State||Published - Jun 1996|
Bibliographical noteFunding Information:
This researchw as supportedb y NIH grants CA43719 and CA01688 and by the Kentucky AgriculturalE xperimentS tation (article number 95-10-042).
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