Association of thioacetamide and ethanol treatment: dolichol and retinol in isolated rat liver cells.
Our aim was to study the distribution of dolichol, dolichol isoprenoids, and retinol in hepatocytes, Kupffer, sinusoidal endothelial and two subfractions of hepatic stellate cells, --Ito-1 and Ito-2--, after chronic treatment of rats for 2 and 4 months with a low dosage of thioacetamide associated with ethanol. Each type of cell responded differently to the two hepatotoxins. Overall, ethanol rarely affected the action of thioacetamide. Some new information emerges with regard to these hepatotoxins in comparison with the effects exerted by each of the drugs separately: treatment with thioacetamide plus ethanol determined an early decrease in dolichol in Kupffer cells (about 13% and 50% after 2 and 4 months, respectively). Moreover, after liver damage, a load of vitamin A evidenced altered percentages of the form of dolichol with eighteen isoprene units; these percentages were modified by all treatments in all cell types. The results confirm that dolichol is the preferred target of oxidative stress and suggest a relationship between dolichol and retinol metabolisms, and a possible new role of dolichol precursors, of prenyltransferases and of retinol metabolites in liver pathology.
Bassi
Anna Maria
AM
Department of Experimental Medicine, Section of General Pathology, University of Genoa, Via L.B. Alberti 2, 16132 Genoa, Italy. patgen@unige.it
Cottalasso
Damiano
D
Canepa
Claudio
C
Maloberti
Giuseppe
G
Casu
Anna
A
Nanni
Giorgio
G
D000818:Animals; D002469:Cell Separation; D004286:Dolichols / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000378:metabolism; D013853:Thioacetamide / Q000633:toxicity*; D014801:Vitamin A / Q000378:metabolism*
D004286:Dolichols; D013729:Terpenes; D013853:Thioacetamide; D014801:Vitamin A; D000431:Ethanol