Lettinga K D, Gutter W, Van Noorden C J, Schellens J P, Frederiks W M
Laboratory of Cell Biology and Histology, University of Amsterdam, Netherlands.
Liver. 1996 Feb;16(1):1-11. doi: 10.1111/j.1600-0676.1996.tb00696.x.
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.
鉴于维生素A补充剂的广泛应用，了解与维生素A过多症相关的潜在毒性变得愈发重要。多年的维生素A过多症最终可能导致肝细胞损伤。在本研究中，用高剂量视黄醇对大鼠进行7天的处理，以利用（酶）组织化学、免疫组织化学和电子显微镜研究其对不同类型肝细胞代谢的早期影响。维生素A的过量摄入会激活库普弗细胞，并诱导贮脂细胞中脂滴的积累以及这些细胞的增殖。此外，它会影响肝小叶中的代谢异质性，但不会导致明显的细胞损伤。根据不同代谢过程标记酶的变化得出结论，嘌呤分解能力、抗氧化能力、吞噬潜力和氨水平调节能力在很大程度上降低。肝细胞中碱性磷酸酶活性的增加表明视黄醇酯通过胆小管膜的转运过程被激活。这些代谢变化的可能原因在讨论中已有描述。
