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International audience; Disruption of iron homeostasis at the levels of intestinal absorption or erythropoiesis contributes to cadmium toxicity. Cellular iron homeostasis in metazoans is maintained by the iron regulatory proteins (IRPs) that regulate the synthesis of proteins involved in the transport, use, and storage of iron. The effect of cadmium intoxication on this regulatory system has been investigated in a cellular model of human epithelium. Cadmium exposure of HeLa cells did not activate the IRPs; rather, the amount of these proteins relative to that of housekeeping proteins decreased. Accordingly, the transferrin receptor mRNA level decreased upon cadmium insult. In a more integrated investigation, separate groups of mice had free access to different doses of cadmium in drinking water for 3 weeks. Cadmium accumulated in all analyzed organs, but its concentration in mouse tissues did not correlate with changes of the activity of the IRPs. The intoxicated mice did not show any sign of anemia, indicating that iron homeostasis was not immediately disrupted after the onset of cadmium accumulation. These data establish that cadmium destabilizes IRPs in mammalian cells, but that iron imbalance is not an early event of cadmium intoxication.

International audience; Practically all human populations are environmentally exposed to cadmium (Cd), mostly through plant-derived food. A growing body of epidemiological evidence suggests that there is no margin of safety between current Cd exposure levels and the threshold for adverse health effects and, hence, there is an urgent need to lower human Cd intake. Here we review recent studies on rice (Oryza sativa) and Cd-hyperaccumulating plants that have led to important insights into the processes controlling the passage of Cd from the soil to edible plant organs. The emerging molecular understanding of Cd uptake, root retention, root-to-shoot translocation and grain loading will enable the development of low Cd-accumulating crops.

This study investigates the effect in rats of acute CdCl2(5 μM) intoxication on renal function and characterizes the transport of Ca2+, Cd2+, and Zn2+in the proximal tubule (PT), loop of Henle (LH), and terminal segments of the nephron (DT) using whole kidney clearance and nephron microinjection techniques. Acute Cd2+injection resulted in renal losses of Na+, K+, Ca2+, Mg2+, PO4−2, and water, but the glomerular filtration rate remained stable.45Ca microinjections showed that Ca2+permeability in the DT was strongly inhibited by Cd2+(20 μM), Gd3+(100 μM), and La3+(1 mM), whereas nifedipine (20 μM) had no effect.109Cd and65Zn2+microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of109Cd were taken up.109Cd fluxes were inhibited by Gd3+(90 μM), Co2+(100 μM), and Fe2+(100 μM) in all nephron segments. Bumetanide (50 μM) only inhibited109Cd fluxes in LH; Zn2+(50 and 500 μM) inhibited transport of109Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute Cd2+intoxication are suggestive of proximal tubulopathy; 2) Cd2+inhibits Ca2+reabsorption possibly through the epithelial Ca2+channel in the DT, and this blockade could account for the hypercalciuria associated with Cd2+intoxication; 3) the PT is the major site of Cd2+reabsorption; 4) the paracellular pathway and DMT1 could be involved in Cd2+reabsorption along the LH; 5) DMT1 may be one of the major transporters of Cd2+in the DT; and 6) Zn2+is taken up along each part of the nephron and its transport in the terminal segments could occur via DMT1.