A method to assess 59Fe in residual tissue blood content in mice and its use to correct 59Fe-distribution kinetics accordingly

Toxicology. 2007 Nov 20;241(1-2):19-32. doi: 10.1016/j.tox.2007.08.082. Epub 2007 Aug 7.

Abstract

Background: 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.

Aim: 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.

Methods: 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).

Results and discussion: 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.

Conclusions: 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.

MeSH terms

  • Animals
  • Blood Volume / physiology
  • Body Weight / physiology
  • Bone Marrow / metabolism
  • Erythrocytes / metabolism
  • Hemoglobins / metabolism
  • Iron / administration & dosage
  • Iron / blood*
  • Iron / pharmacokinetics*
  • Iron Radioisotopes / administration & dosage
  • Iron Radioisotopes / blood*
  • Iron Radioisotopes / pharmacokinetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nonheme Iron Proteins / metabolism
  • Nutritional Status
  • Organ Size / physiology
  • Regional Blood Flow / physiology
  • Tissue Distribution

Substances

  • Hemoglobins
  • Iron Radioisotopes
  • Nonheme Iron Proteins
  • Iron