title: Early effects of high doses of retinol (vitamin A) on the in situ cellular metabolism in rat liver.
abstract: Understanding of the possible toxicity associated with hypervitaminosis A becomes increasingly important in view of the popularity of vitamin A supplementation. Hypervitaminosis A for many years may eventually lead to hepatocellular damage. In the present study, rats were treated for 7 days with high doses of retinol to study the early effects on the metabolism of different types of liver cells using (enzyme) histochemistry, immunohistochemistry and electron microscopy. Excessive intake of vitamin A activates Kupffer cells and induces accumulation of lipid droplets in fat-storing cells as well as proliferation of these cells. Moreover, it affects the metabolic heterogeneity in the liver lobules, but does not lead to apparent cell damage. Based on the changes in marker enzymes for different metabolic processes, it is concluded that the capacity for breakdown of purines, the antioxidant capacity, the potential for phagocytosis and the regulation of ammonia levels were largely decreased. Increased alkaline phosphatase activity in hepatocytes pointed to an activated process of transport of retinol esters over the bile canalicular membrane. The possible causes of these metabolic changes have been described in the discussion.
authors.affiliation: Laboratory of Cell Biology and Histology, University of Amsterdam, Netherlands.
authors.forename: K D
authors.initials: KD
authors.lastname: Lettinga
authors.forename: W
authors.initials: W
authors.lastname: Gutter
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Noorden
authors.forename: J P
authors.initials: JP
authors.lastname: Schellens
authors.forename: W M
authors.initials: WM
authors.lastname: Frederiks
mesh_terms: D000818:Animals; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006986:Hypervitaminosis A / Q000378:metabolism*; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000378:metabolism / Q000648:ultrastructure; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D014801:Vitamin A / Q000008:administration & dosage*
chemical_list: D008112:Liver Glycogen; D014801:Vitamin A; D005954:Glucosephosphate Dehydrogenase