Our line of researches follows the hypothesis that
dolichol and
retinol metabolism might be interrelated and involved in
liver fibrosis. To this end, in this study rats were subjected to chronic treatment with
thioacetamide (TAA) (300 mg/L liquid diet) for 1 and 2 months and, after liver damage had occurred, supplemented with
vitamin A before sacrifice.
Dolichol,
dolichol isoprene units, and
retinol content were determined in isolated parenchymal and sinusoidal liver cells (hepatic stellate cells; Kupffer cells; sinusoidal endothelial cells).
Dolichol increased in hepatocytes after TAA treatment, with or without
vitamin A.
Dolichol decreased in the other cells.
Retinol in general decreased. In hepatocytes,
retinol decreased only on normal nutrition, while the
vitamin A load was taken up normally. The percentages of
dolichol isoprene units (Dol-16 to Dol-20, in rats) confirm that Dol-18, which was not modified in percentage by TAA on normal nutrition, did not increase after
vitamin A, as it did in control cells (7-12%). The behavior of Dol-18 was similar in all the cells studied.
Vitamin A might reveal a latent damage produced by TAA on
dolichol homologues. These data support previous hypotheses that the action of TAA depends on the administration modality, the dosage, and the diet, and that Dol-18 might have different functions and compartmentalization in the cells. Furthermore, the results support the hypothesis that
dolichol chain length might be interrelated with
retinol metabolism, perhaps through their metabolites.