Effects of tiadenol and di-(2-ethylhexyl)phthalate on the metabolism of phosphatidylcholine and phosphatidylethanolamine in the liver of rats: comparison with clofibric acid.

Metabolic changes induced by 2,2'-(decamethylenedithio)diethanol (tiadenol) and di-(2-ethylhexyl)phthalate (DEHP) in the biosynthesis of phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) in rat liver were compared with changes induced by p-chlorophenoxyisobutyric acid (clofibric acid). Treatment of rats with either tiadenol or DEHP increased the hepatic contents of PtdCho and PtdEtn, as was observed with clofibric acid treatment. The administration of tiadenol, DEHP, or clofibric acid slightly, but significantly, increased, in common, the activity of CTP:phosphocholine cytidylyltransferase, a key enzyme for the synthesis de novo of PtdCho, and suppressed the activity of PtdEtn N-methyltransferase. With regard to the enzymes involved in the synthesis of PtdEtn, the three peroxisome proliferators enhanced the activity of phosphatidylserine (PtdSer) decarboxylase and markedly decreased the activity of CTP:phosphoethanolamine cytidylyltransferase. Treatment of rats with the three compounds markedly increased, in common, the content and the proportion of the molecular species of PtdCho containing oleic acid (18:1), but considerably decreased the proportion of the molecular species of PtdCho containing linoleic acid (18:2) in the liver, resulting in a striking decrease in the concentration of the molecular species of PtdCho containing 18:2 in the serum. The present study suggests that the administration of peroxisome proliferators to rats increases the contents of hepatic PtdCho and PtdEtn for hepatomegaly and proliferation of organelles by the same mechanism, irrespective of their chemical structures.