Sato Kei, Taniai Masamitsu, Kato Kota, Kato Takashi
Faculty of Education and Integrated Arts and Sciences, Waseda University, 2-2 Wakamatsu-Cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Major in Integrative Bioscience and Biomedical Engineering, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-Cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Zoolog Sci. 2020 Feb;37(1):61-69. doi: 10.2108/zs190102.
Iron is an essential element for hemoglobin synthesis during erythropoiesis. Iron overload, in contrast, adversely affects erythropoiesis and causes organ dysfunction. Research using various animal models may help to elucidate pathophysiological mechanisms induced by excess iron. In the present study, we evaluated the relationship between iron metabolism and erythropoietic activity in the African clawed frog, . In , both erythropoiesis and iron metabolism occur in the liver. First, we developed a method to quantify iron levels in the liver and plasma using 2-nitroso-5-[N-n-propyl-N-(3-sulfopropyl) amino] phenol (Nitroso-PSAP). We then measured iron levels and analyzed hematopoietic parameters in frogs that were orally administered sodium ferrous citrate (SFC). The hepatic iron level increased in the SFC group, but the number of erythrocytes, hematocrit, and hemoglobin concentration did not change, suggesting that the regulation of the production and release of mature erythrocytes in the liver was not directly affected by dietary iron. At four days after administration of 2 mg/kg SFC, the number of immature erythrocytes decreased in the liver. Interestingly, atypical blood cells with hyper-segmented nuclei were observed, identified by acridine orange cell staining; these atypical blood cells were hardly detectable under the steady state. Compared with previously reported results in mice, the increase in the hepatic iron levels was small, but our results indicate that SFC affects hematopoietic activity. These results establish a novel model for iron metabolism and provide new insights into the relationship between iron metabolism and erythropoiesis in vertebrates.
铁是红细胞生成过程中血红蛋白合成所必需的元素。相比之下，铁过载会对红细胞生成产生不利影响，并导致器官功能障碍。使用各种动物模型进行的研究可能有助于阐明铁过量引发的病理生理机制。在本研究中，我们评估了非洲爪蟾体内铁代谢与红细胞生成活性之间的关系。在非洲爪蟾中，红细胞生成和铁代谢均发生于肝脏。首先，我们开发了一种使用2-亚硝基-5-[N-正丙基-N-(3-磺丙基)氨基]苯酚（亚硝基-PSAP）来定量肝脏和血浆中铁水平的方法。然后，我们测量了口服柠檬酸亚铁钠（SFC）的青蛙的铁水平，并分析了造血参数。SFC组的肝脏铁水平升高，但红细胞数量、血细胞比容和血红蛋白浓度并未改变，这表明肝脏中成熟红细胞的产生和释放调节并未直接受到饮食中铁的影响。在给予2 mg/kg SFC四天后，肝脏中未成熟红细胞数量减少。有趣的是，通过吖啶橙细胞染色鉴定出了具有核超分叶的非典型血细胞；在稳态下几乎检测不到这些非典型血细胞。与先前在小鼠中报道的结果相比，肝脏铁水平的升高幅度较小，但我们的结果表明SFC会影响造血活性。这些结果建立了一个新的铁代谢模型，并为脊椎动物中铁代谢与红细胞生成之间的关系提供了新的见解。
