Study on the mechanisms of vitamin A-storage in arctic animals

由于外源性物质可降低维生素A毒性的阈值，并且维生素A和脂溶性外源性物质都有在食物链中积累的趋势，我们对斯瓦尔巴群岛哺乳动物和鸟类肝脏维生素A储存进行了系统的表征，并在这些动物中寻找维生素A相关毒性的迹象。包括北极熊、北极狐、须海豹和白鸥在内的顶级捕食者的维生素A含量比所有其他研究的北极动物以及与它们基因相关的大陆顶级捕食者高出约10-20倍。与正常人和实验动物如小鼠和大鼠相比，这些值也很高。大量的肝脏维生素A位于肝星状细胞中的大的自发荧光脂滴中。这些液滴构成了大部分细胞的细胞质。在肝星状细胞中这种有效的维生素A储存机制的发展可能有助于顶级捕食者在北极极端环境中的生存。这些动物既没有表现出维生素A过多的迹象，也没有肝脏的病理发现。北极熊和髯海豹的肾脏总视黄醇（可用作维生素A相关毒性或过量的指标）低于其肝脏值的1%，这在大多数动物的正常范围内。然而，北极狐和银鸥的肾脏水平分别约为肝脏值的9%和42%。北极狐和白鸥肾脏中总视黄醇浓度的增加很可能是维生素A中毒的一个迹象，值得关注。这一观察结果令人担忧，以前在自由生活的动物中没有观察到。对年龄较大的食肉动物的样本进行分析，这些食肉动物随着时间的推移可能积累了更多的维生素A和有机污染物，这可能会澄清这些和其他维生素A毒性的迹象是否存在于这些动物中。

As xenobiotics may reduce the threshold of vitamin A-toxicity and both vitamin A and fatsoluble xenobiotics have a tendency to accumulate in the food chain, we have perfomied a systematic characterization of the hepatic vitamin A-storage in mammals and birds of the Svalbard archipelago and searched for sign of vitamin A-related toxicity in these animals. The top predators including polar bear, arctic fox, bearded seal and glaucous gull contained about 10-20 times more vitamin A than all other arctic animals studied as well as their genetically related continental top predators. The values are also high compared to normal human and experimental animals like mouse and rat. This massive amount of hepatic vitamin A was located in large autofluorescent lipid droplets in hepatic stellate cells. The droplets made up most of the cells' cytoplasm. The development of such an efficient vitamin A-storing mechanism in the hepatic stellate cells may have contributed to the survival of top predators in the extreme environment of the Arctic. These animals demonstrated neither sign of hypervitaminosis A nor pathological findings in the liver.Kidney total retinol, which may be used as a biomarke for vitamin A-related toxicity or excess, in polar bear and bearded seal were below 1% of their liver value, Which is in the normal range for most animals. Arctic fox and glaucous gull, however, had kidney levels of about 9 and 42% of the liver values, respectively. This increased kidney concentrations of total retinol in arctic fox and glaucous gull is most likely a sign of vitamin A-toxicity that deserved attention. This observation is alarming and has not been observed previously in free-living animals. Analysis of samples from older predators who over time may have accumulated more of vitamin A and organic pollutants may clarify whether these and other signs of vitamin Atoxicity is present in such animals.