Prevention by dietary (n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced by cyclosporine A in animals.
Previous findings showed that dietary (n-6) polyunsaturated phosphatidylcholines (vegetable lecithin) could efficiently prevent intrahepatic cholestasis induced by cyclosporine A in rats. Mechanistic studies showed that expressions in rat liver of Na(+), K(+)-ATPase, Ca(2+), Mg(2+)-ATPase and F-actin were both decreased by drug administration and both enhanced by (n-6) lecithin enriched diet. There is a possible direct effect of phosphatidylcholines, vectors of polyunsaturated fatty acids provided by the metabolism of the dietary lecithin, on the aforesaid hepatic parameters. Such modulations by drug and diet result in reversed modifications of membrane composition and fluidity. Final outcome is decreased and enhanced bile lipid secretion by cyclosporine and vegetable lecithin enriched diet respectively. Moreover, we advance the hypothesis of a bypass process including a separate and functional actin-independent way for the non micellar and phospholipid-dependent secretion of bile lipids. The relationships between the ATPases, the microfilament components such as F-actin and the different transporters still remain to be clarified. Furthermore, one can speculate on beneficial effects in humans of diets enriched in vegetable lecithins that might prevent cholestasis induced by cyclosporine A.
Chanussot
Françoise
F
INSERM U. 476, Faculté de Médecine, 27 bd Jean Moulin, 13385 Marseille cedex 05, France. Francoise.Chanussot@medecine.univ-mrs.fr
Benkoël
Liliane
L
D000199:Actins / Q000096:biosynthesis / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002779:Cholestasis / Q000517:prevention & control*; D016572:Cyclosporine / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000517:prevention & control*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D000960:Hypolipidemic Agents; D010713:Phosphatidylcholines; D010743:Phospholipids; C029449:polyene phosphatidylcholine; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D008274:Magnesium; D002118:Calcium