Schümann Klaus, Szegner Bernadett, Kohler Birgit, Pfaffl Michael W, Ettle Thomas
Wissenschaftszentrum Weihenstephan, Technische Universität München, Germany.
Toxicology. 2007 Nov 20;241(1-2):19-32. doi: 10.1016/j.tox.2007.08.082. Epub 2007 Aug 7.
Dysregulation of body iron-distribution may induce oxidative damage. To investigate the molecular mechanisms of iron homeostasis, corresponding essential genes are manipulated by many working groups. This asks for a simple method to pursue the resulting impact on body iron-distribution in mice.
To develop a method for the assessment of (59)Fe in residual tissue blood content and to correct this influence in (59)Fe body distribution studies.
Iron status in male adult C57BL6 mice was adjusted by feeding diets with different iron content. Fractional contribution of organs to total body weight was determined after dissection. (59)Fe-labelled blood was injected in recipient mice to estimate total blood volume and residual blood content in all organs and tissues. The main experiment used these data to correct total (59)Fe tissue content at six intervals after (59)Fe injection (12h-28 days).
The sum of (59)Fe in all organs was the same as determined in each mouse before dissection. (59)Fe in whole blood remained constant from the 4th day after injection on, and was highest in iron-deficiency. As in other species, residual blood content was highest in spleen and lungs. Nevertheless, (59)Fe in the iron-deficient spleen decreased to zero and intestinal (59)Fe-content also decreased significantly over time after correction for (59)Fe in residual blood. These findings suggest correct assessment of compartment sizes and (59)Fe in residual blood in each organ.
Differences in (59)Fe-distribution between iron status reflected changes in the expression of proteins of iron-transport and its regulation correctly. Thus, the method seems suitable to analyse body iron-distribution in consequence to genetic manipulations of murine iron homeostasis which is a prerequisite to assess possible toxicological consequences of iron supplementation.
机体铁分布失调可能会引发氧化损伤。为了探究铁稳态的分子机制，许多研究团队对相应的关键基因进行了调控。这就需要一种简单的方法来追踪对小鼠机体铁分布产生的影响。
开发一种评估残余组织血中铁含量的方法，并在59Fe机体分布研究中校正这种影响。
通过喂食不同铁含量的饲料来调节成年雄性C57BL6小鼠的铁状态。解剖后测定各器官对总体重的贡献率。向受体小鼠注射59Fe标记的血液，以估算所有器官和组织中的总血容量和残余血含量。主要实验利用这些数据在注射59Fe后6个时间点（12小时至28天）校正总59Fe组织含量。
所有器官中59Fe的总和与解剖前每只小鼠体内测定的结果相同。注射后第4天起全血中的59Fe保持恒定，缺铁时含量最高。与其他物种一样，脾脏和肺中的残余血含量最高。然而，校正残余血中的59Fe后，缺铁脾脏中的59Fe降至零，肠道59Fe含量也随时间显著下降。这些发现表明需正确评估每个器官中残余血的腔室大小和59Fe含量。
不同铁状态下59Fe分布的差异正确反映了铁转运蛋白及其调控蛋白表达的变化。因此，该方法似乎适用于分析小鼠铁稳态基因操作对机体铁分布的影响，这是评估铁补充可能产生的毒理学后果的前提条件。
