Subcellular changes of essential metal shown by in-air micro-PIXE in oral cadmium-exposed mice

Abstract

To clarify the relation of essential metals to cadmium (Cd) toxicity, we evaluated metallothionein expression and analyzed the subcellular distribution of essential metals using in-air micro-Particle-Induced X-ray Emission (PIXE). Four mice were dosed orally with 100 mg/L of Cd in drinking water for 1.5 or 2 years. Frozen samples of organs were used for micro-PIXE analysis and formalin-fixed samples were used for metallothionein staining. Immunohistochemically, metallothionein induction by 1.5y-Cd exposure was higher in the renal cortex than in the liver. Metallothionein expression was reduced after 2y-Cd administration compared to the 1.5y-Cd-exposed mice. Cd-induced tissue damage became marked in the 2y-Cd-exposed mice compared to the 1.5y-Cd-exposed mice, in which nephrotoxicity was more prominent than hepatotoxicity. Cd yield was higher in the renal cortex of the 2y-Cd-exposed mouse than in that of the 1.5y-Cd-exposed mouse, whereas no such increasing tendency was found in the liver. Compared to the control, the Cd-exposed mice markedly accumulated zinc in the liver and renal cortex. In the Cd-exposed mice, iron was mildly accumulated in the renal cortex and was slightly deprived in the liver. Elemental maps showed that a large amount of Cd was spatially combined with zinc in the 1.5y-Cd mouse. Free Cd became abundant in the 2y-Cd-exposed mouse. In addition, a small amount of Cd was colocalized with iron. The data suggest that zinc may contribute to protect against oral-administrated Cd toxicity, and impaired induction of MT may participate in hepato-nephrotoxicity of the 2y-Cd-exposed mouse.

Protective Effect of Zinc (Zn) on the Histology and Histochemistry of Liver and Kidney of Albino Rat Treated with Cadmium

“…In agreement with a large number of studies who noted similar or more pronounced changes in the hepa tic and renal tissues under Cd effect [2,9,11,[20][21][22][23][24]. Our results indicated significant CdCl 2 toxic effects on the liver and kidney structures.…”

The effect of dietary selenium supplementation on cadmium absorption and retention in suckling rats

“…2) are in accordance with reported Cd-induced changes in Zn homeostasis (Brzóska and Moniuszko-Jakoniuk 2001;Bridges and Zalups 2005;Nakazato et al 2008). We can not provide a good explanation for the elevated Fe level after Se supplementation, as no significant interaction between these elements was reported in the literature.…”

Changes of the mRNA Expression Pattern of Zn Transporters: a Probable Mechanism for Cadmium Retention and Zinc Redistribution in the Suckling Rat Tissues

“…The present study shows that Cd exposure during lactation decrease significantly the neonatal Zn absorption and leads to Zn redistribution in suckling rat organism, with increase in its total content in the liver and kidneys and its depletion in the gastrointestinal tract (stomach content and intestine) and plasma. These results are in accordance with reported Cd-induced changes in Zn homeostasis [8,29]. In the present study, it is not possible to distinguish between endogenous and exogenous Zn.…”