No abstract

The major route of cadmium (Cd) intake by non-smokers is through food ingestion. Cd is a non-essential metal absorbed through one or more transporters of essential metal ions. Expression of these transporters is affected by nutritional status. To investigate the risk factors for Cd toxicity, the effects of deficiency of essential metals on hepatic and renal accumulation of Cd were studied in mice of different ages. Mice were administered a control diet or one of the essential metal-deficient diets, administered Cd by gavage for 6 weeks, and killed; then, Cd accumulation was evaluated. Iron deficiency (FeDF) or calcium deficiency (CaDF) resulted in remarkable increases in hepatic and renal Cd accumulation compared with control-diet mice and other essential metal-deficient mice. Cd accumulation in hepatic and renal tissue was increased significantly at all ages tested in FeDF and CaDF mice. Renal Cd concentrations were higher in 4-week-old mice than in 8-and 25-week-old mice. Increase in intestinal mRNA expression of calcium transporter (CaT)1, divalent metal ion transporter-1, and metallothionein (MT)1 was also higher in 4-week-old mice than in other mice. Renal accumulation of Cd showed strong correlation with intestinal mRNA expression of CaT1 and MT1. These data suggest that CaDF and FeDF at younger ages can be a risk factor for Cd toxicity.Key words cadmium; age-related risk factor; essential metal-deficiency; intestinal metal transporter Cadmium (Cd) is a non-essential metal that can pollute soils. Cd can contaminate food and water, enter the body, bind to metallothioneins (MTs), and accumulate in target organs (e.g., liver, kidneys). Dietary intake (rather than elimination) of Cd is one of the main variables for determination of the body burden of Cd. Studies using experimental animals have shown that 0.5-8% of administered cadmium nitrate or cadmium chloride is absorbed.1) Factors that can cause fluctuations in Cd absorption include: animal species; type of Cd compound; dose and frequency of administration; interactions with various nutrients or drugs; nutritional status; age; sex; life stage such as gestation and lactation.The nutritional status of essential metals (EMs) can affect the kinetics of EMs and non-essential metals (including Cd). Rats fed minimal amounts of zinc (Zn), iron (Fe), and calcium (Ca) have been shown to simultaneously retain up to eight times more 109 Cd than rats fed adequate amounts of minerals.2) Cd can be absorbed through two main transporters: divalent metal transporter (DMT)1 and calcium transporter (CaT) Park et al. suggested that Fe depletion increases apical influx of Cd in the small intestine by upregulation of the mRNA expression of DMT1. 4) Studies in rats have demonstrated a strong correlation between Cd absorption and duodenal expression of DMT1 as well as the basolateral efflux of ferroportin-1. Affinity between Cd and DMT1 is higher than that between Fe and DMT1, and Cd is transferred instead of Fe in a DMT1-overexpressed condition.5) This evidence suggests that DMT1...