Spatial localization of cadmium and metallothionein in the kidneys of mice at the early phase of cadmium accumulation

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  • Fujishiro Hitomi
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
  • Sumino Miharu
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
  • Sumi Daigo
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
  • Umemoto Hitomi
    Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Tsuneyama Koichi
    Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Matsukawa Takehisa
    Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine
  • Yokoyama Kazuhito
    Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine Department of Epidemiology and Social Medicine, Graduate School of Public Health, International University of Health and Welfare
  • Himeno Seiichiro
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University

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<p>Chronic exposure to cadmium (Cd) leads to an accumulation of Cd in the kidneys. Metallothionein (MT) is a low-molecular-weight protein having a high affinity for Cd. Cd bound to MT in serum is filtered through the glomeruli of kidney nephrons and reabsorbed by endocytosis into the proximal tubules from the luminal side. Accumulation of Cd in renal cells induces MT synthesis, leading to long-term deposition of Cd and the suppression of Cd toxicity. Recently, many studies have investigated the tissue distribution of metals using laser ablation ICP-MS (LA-ICP-MS). However, little information has been available regarding renal Cd distribution. Hence, we dually investigated the renal distribution of Cd by LA-ICP-MS and that of MT by immunohistochemistry to clarify the dose- and time-dependent changes in the distributions of Cd and MT in mice exposed to Cd from drinking water for 1, 2, and 4 months. Both Cd and MT exhibited characteristic heterogeneous distribution patterns in the renal cortex. The accumulation of Cd and MT near the surface of the cortex suggests a preferential accumulation of Cd in the surface nephrons. MT distribution was more pronounced in the proximal tubules than in the distal tubules, and there were clear differences in MT immunostaining even among the proximal tubules. The heterogeneous localization of MT may reflect the nephron-specific accumulation of Cd. Combining elemental imaging of Cd with immunostaining of MT proved a successful strategy to reveal the characteristic renal Cd distribution, especially in the early stages of Cd accumulation.</p>

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