Matsuo-Tezuka Yukari, Noguchi-Sasaki Mariko, Kurasawa Mitsue, Yorozu Keigo, Shimonaka Yasushi
Product Research Department, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, 247-8530, Kanagawa, Japan.
Int J Hematol. 2017 Jul;106(1):60-70. doi: 10.1007/s12185-017-2215-3. Epub 2017 Mar 14.
Erythropoiesis-stimulating agents are among the therapeutic options for renal anemia. Under erythropoietic stimulation, the synthesis of hemoglobin requires a large amount of iron, which is supplied both from absorption of dietary iron and the mobilization of stored iron. However, under iron-loading conditions, dietary iron absorption is suppressed via down-regulation of duodenal iron transporters. Because the contribution of dietary iron is essential for erythropoiesis, we aimed to investigate the conditions in which dietary iron is efficiently used for erythropoiesis. To quantify the contribution of dietary iron for erythropoiesis, we labelled dietary iron using the stable iron isotope Fe, and assessed Fe-derived hemoglobin synthesis under erythropoietic stimulation by C.E.R.A. (Continuous Erythropoietin Receptor Activator) and iron loading in mice. Our results show that the contribution of dietary iron to erythropoiesis is not changed by different increments of C.E.R.A. dose. However, iron loading suppressed the contribution of dietary iron to erythropoiesis. To confirm these results under conditions mimicking clinical settings, we compared single and intermittent administration of C.E.R.A. in mice under both physiological and iron-loaded conditions, and found that the contribution of dietary iron to erythropoiesis is more strongly affected by body iron status than by erythropoietic stimulation.
促红细胞生成素是肾性贫血的治疗选择之一。在促红细胞生成刺激下，血红蛋白的合成需要大量铁，这些铁既来自膳食铁的吸收，也来自储存铁的动员。然而，在铁负荷条件下，十二指肠铁转运蛋白下调会抑制膳食铁的吸收。由于膳食铁对红细胞生成至关重要，我们旨在研究膳食铁有效用于红细胞生成的条件。为了量化膳食铁对红细胞生成的贡献，我们使用稳定铁同位素Fe标记膳食铁，并评估在促红细胞生成素受体持续激活剂（C.E.R.A.）促红细胞生成刺激和小鼠铁负荷情况下源自Fe的血红蛋白合成。我们的结果表明，不同剂量递增的C.E.R.A.不会改变膳食铁对红细胞生成的贡献。然而，铁负荷会抑制膳食铁对红细胞生成的贡献。为了在模拟临床环境的条件下证实这些结果，我们比较了在生理和铁负荷条件下小鼠单次和间歇给予C.E.R.A.的情况，发现膳食铁对红细胞生成的贡献受机体铁状态的影响比对促红细胞生成刺激的影响更大。
