Mallia A K, Smith J E, Goodman D W
J Lipid Res. 1975 May;16(3):180-8.
Vitamin A is normally transported in plasma as retinol bound to a specific protein, retinol-binding protein (RBP). Detailed studies were conducted to examine the effects of excess vitamin A on the plasma concentration and metabolism of RBP, and to obtain information about vitamin A transport in the hypervitaminotic state. Two separate experiments were conducted. In the first (Study I, 99 days), plasma RBP and vitamin A levels were compared in three groups of rats fed 0.14 mg (control), 7.3 mg (group 2), or 41 mg (group 3) of vitamin A per day. After day 50 of the study, the administration of excess vitamin A to hypervitaminotic rats (groups 2 and 3) was discontinued and the rats were allowed to recover from vitamin A toxicity. In the second, shorter experiment (Study II), serum vitamin A and RBP levels were compared in control and hypervitaminotic (34 mg of retinyl acetate per day) rats. The rats in this study were also given [3-H]retinyl acetate daily to determine the distribution of retinyl esters and retinol between the lipoprotein and nonlipoprotein protein fractions of plasma. In both studies, administration of large, excessive doses of vitamin A resulted in substantial and significant decreases in the levels of serum RBP. Excessive doses of vitamin A produced fatty liver in the rats, in association with a normal (group 2, Study I) or with a decreased (group 3, Study I) level of RBP in the liver. It is possible that excess vitamin A leads to decreased rates of RBP synthesis in, and of RBP secretion from, the liver. Administration of excessive doses of vitamin A also resulted in elevations of serum vitamin A levels, which were mainly due to large increases in the circulating levels of retinyl esters. In the hypervitaminotic rats, most of the serum vitamin A, and virtually all of the retinyl esters, was found in association with the serum lipoproteins of hydrated density less than 1.21. These results demonstrate that the serum lipoproteins play an important role in the transport of the vitamin A that accumulates in serum in hypervitaminosis A. We suggest that the toxic manifestations of hypervitaminosis A occur when vitamin A circulates in plasma and is presented to membranes in a form other than bound to RBP. Plasma lipoproteins may nonspecificially deliver vitamin A to biological membranes and hence lead to vitamin A toxicity.
维生素A通常在血浆中作为与特定蛋白质——视黄醇结合蛋白（RBP）结合的视黄醇进行运输。开展了详细研究以检测过量维生素A对RBP血浆浓度及代谢的影响，并获取高维生素A状态下维生素A运输的相关信息。进行了两项独立实验。在第一项实验（研究I，为期99天）中，比较了三组每天分别摄入0.14毫克（对照组）、7.3毫克（第2组）或41毫克（第3组）维生素A的大鼠的血浆RBP和维生素A水平。在研究第50天后，停止向高维生素A大鼠（第2组和第3组）投喂过量维生素A，让大鼠从维生素A毒性中恢复。在第二项较短的实验（研究II）中，比较了对照组和高维生素A（每天34毫克醋酸视黄酯）大鼠的血清维生素A和RBP水平。该研究中的大鼠还每天给予[3-H]醋酸视黄酯，以确定视黄酯和视黄醇在血浆脂蛋白和非脂蛋白部分之间的分布。在两项研究中，给予大剂量过量维生素A均导致血清RBP水平大幅显著下降。过量维生素A使大鼠产生脂肪肝，同时肝脏中RBP水平正常（研究I第2组）或降低（研究I第3组）。过量维生素A可能导致肝脏中RBP合成速率及从肝脏分泌的RBP速率降低。给予过量维生素A还导致血清维生素A水平升高，这主要是由于循环中视黄酯水平大幅增加。在高维生素A大鼠中，大部分血清维生素A以及几乎所有视黄酯都与水合密度小于1.21的血清脂蛋白相关。这些结果表明，血清脂蛋白在高维生素A血症中血清中积累的维生素A的运输中起重要作用。我们认为当维生素A在血浆中循环并以未与RBP结合的形式呈现给细胞膜时，就会出现高维生素A血症的毒性表现。血浆脂蛋白可能会非特异性地将维生素A递送至生物膜，从而导致维生素A毒性。
