Interaction between monensin and CCl4 after chronic treatment: Dolichol and retinol content of rat liver sinusoidal cells

The aim of this investigation was to study retinol, which is known to decre ase in hepatic stellate cells during fibrogenesis, and dolichol, which infl uences membrane fluidity and decreases in liver injury, in freshly isolated liver parenchymal and nonparenchymal cells after intoxication of rats with CCl4 combined with the ionophore monensin for 3, 5 and 7 weeks. To study t he interrelationship between dolichol and vitamin A transport, a load of vi tamin A was given to batches of rats 3 days before sacrifice. Monensin did not modify the action of CCl4 in hepatocytes. On administration of CCl4 and CCl4-monensin, dolichol decreased independently of vitamin A load, while r etinol increased, especially when a load of vitamin A was given to rats 3 d ays before sacrifice. Hepatocytes appeared to no longer be able to export o r metabolize vitamin A. In a subfraction of hepatic stellate cells (Ito-l c ells) dolichol always decreased, while retinol was no longer stored after e ach trealment; dolichol and retinol showed the same behavior but the decrea se was more pronounced in monensin after vitamin A load and after 3 weeks. These data support the hypothesis that by modulating membrane characteristi cs, dolichol might be involved in intracellular or intercellular retinol tr ansport and that altered transport between hepatocytes and Ito-1 cells migh t accompany liver injury: The data regarding another subfraction, Ito-2 cel ls, partly resemble those for the Ito-1 fraction and are in agreement with the heterogeneity of hepatic stellate cells. In Kupffer and sinusoidal endo thelial cells, dolichol and retinol content was not homogeneous and was onl y slightly altered after the treatments. Monensin and CC!, are not interact ive. Although both drugs alter membrane lipids, their association allows so me sinusoidal cell responses to be differentiated.