Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/20/2004
Publication Date: 1/1/2005
Citation: Reeves, P.G., Chaney, R.L., Simmons, R.W., Cherian, M.G. 2005. Metallothionein induction is not involved in cadmium accumulation in the duodenum of mice and rats fed diets containing high-cadmium rice or sunflower kernels and a marginal supply of zinc, iron, and calcium. Journal of Nutrition. 135:99-108. Interpretive Summary: Cadmium is a toxic trace element found in most foods. Work in our laboratory shows that low intakes of natural minerals nutrients such as zinc, iron, and calcium increase cadmium absorption 10-fold. Some grains, such as polished rice do not contain high amounts of these mineral nutrients, but if grown in polluted paddies, it can have high amounts of cadmium. People who consume this rice as a staple food would absorb more cadmium unless they also consume adequate amounts of the other minerals. In earlier studies, we found that rats that eat diets with low zinc, iron, and calcium accumulate cadmium in the intestinal cells at a high level. The current study was designed to determine whether metallothionein, a natural metal binding protein, was induced in the intestine to account for this increase in cadmium. Results showed that rats consuming a marginal amount of zinc, iron, and calcium had higher cadmium in the upper part of the intestine than rats fed an adequate supply of these minerals, but the amount of metallothionein was unchanged. This suggests the presence of an unknown metal binding protein in these rats. In addition, it was determined whether natural cadmium in rice grown in contaminated paddies was more or less available for absorption than cadmium added during cooking. It was found that cadmium availability was not different between the two treatments. The next discovery was that rice cadmium was as much as 3 times more available for absorption than cadmium from sunflower kernels, even though the amount of cadmium in each food was the same. The results support our previous suggestion that foods differ in mineral availability, and that marginal deficiencies of Fe, Zn, and Ca, commonly found in certain human populations subsisting on rice-based diets, could influence the risk of disease from dietary Cd exposure.
Technical Abstract: It was reported earlier that rats supplied with dietary concentrations of cadmium (Cd) similar to that found in human diets, and marginal concentrations of dietary iron (Fe), zinc (Zn), and calcium (Ca) absorb more Cd into the body and retain up to tenfold more Cd in the duodenum than rats fed adequate mineral diets. The rats were fed rice-based diets extrinsically labeled with Cd. The preceding results raised two questions: 1) what role does intestinal metallothionein (MT) play in the accumulation of duodenal Cd? 2)Is endogenous rice grain Cd equally as available as Cd extrinsically incorporated into the grain? To answer these questions, two experiments were performed. In the first experiment, wild-type and MT-null mice were fed diets containing nutritionally marginal or adequate amounts of Fe, Zn, and Ca. The diets contained 40% rice and provided 240 µg Cd/kg diet. In both wild-type and MT-null mice fed the marginal mineral diets, duodenal Cd was 10 times higher than in similar mice fed adequate mineral diets. These results indicate that MT induction is not involved in duodenal Cd accumulation in animals with marginal dietary status of Fe, Zn, and Ca. In the second experiment, rats were fed diets containing either 40% rice containing Cd incorporated during growth and maturation of the plant, or 40% rice containing Cd incorporated during cooking. Each rice-fed group also was fed either marginal or adequate amounts of Zn, Fe, and Ca. After 5 weeks, rats were given a single meal labeled with 109Cd, and the amount of label retained after 7 days was determined by whole-body-counting. The results showed that rats with marginal mineral status retained 90 times more 109Cd than those with adequate status; however, there was no difference in retention between rats fed the intrinsically or extrinsically labeled rice. Separate groups of rats were fed diets containing 20% roasted sunflower kernels (SFK) with or without adequate Zn, Fe, and Ca and similar amounts of Cd as in the rice diets. SFK fed rats retained only 40% as much 109Cd in their bodies as rice-fed rats, but SFK-fed rats with marginal mineral-status retained 13 times more 109Cd than rats with adequate mineral status. These experiments support the hypothesis that marginal deficiencies of Fe, Zn, and Ca, which are commonly found in certain human populations subsisting on rice-based diets, can play an important role in increasing the risk of dietary Cd exposure.