Calcium-Cadmium Interactions

Recent evidence suggests that chemical-induced cell injury and death may result from impaired regulation of calcium (Corcoran and Ray 1992). Metals may exert their toxicity by interfering with calcium signal transduction proteins, thus interfering with normal cell communication, growth, and differentiation (Rossi et al. 1991). Cadmium stimulates release of calcium from intracellular storage sites and increases levels of inositol triphosphates (Smith et al. 1989). This release of calcium may be related to the interaction of cadmium with a plasma membrane sialoprotein receptor (Chen and Smith 1992). 

Calmodulin is a major intracellular calcium-binding protein which regulates a wide variety of calcium-dependent processes (Cheung 1982). The binding of calcium to calmodulin induces a conformational change in the protein to an active form. The calcium-calmodulin complex is then capable of regulating a host of other molecules such as phosphodiesterase, adenylate kinase, protein kinases, and Ca-ATPase. Cadmium has been shown to 

---

Franklin, N.M., C.N. Glover, J.A. Nicol, et al. 2005. Calcium/cadmium interactions at uptake surfaces in rainbow trout Waterborne versus dietary routes of exposure. Environ. Toxicol. Chem. 24 2954-2964. 

The severe bone demineralization observed in elderly women with low calcium intake and many years of exposure to cadmium suggests a calcium-cadmium interaction. In a variety of studies it has been shown that low calcium intake increases cadmium absorption. 

Osteomalacia and osteoporosis are reported primarily in patients (95% females) with itai-itai disease, and osteomalacia has been observed in cadmium industry workers, the majority of whom are male (Goyer 1991). While the mechanisms for these effects are not well known, cadmium disruption of calcium metabolism may be important. One of the manifestations of renal injury in cadmium-exposed populations is calcuria and negative calcium balance. It is not clear whether these effects on calcium metabolism occur secondary to renal injury, or whether there is a direct effect on calcium pathways (see discussion of calmodulin-calcium-cadmium interactions in Sect. B.I). 

Toxicity due to insufficient MTs depends on factors such as age, gender, and health status. Young mice were found to have a fourfold greater accumulation of cadmium in their brains than adult mice, and significantly less metallothionein. Because cadmium interacts with calcium, women may lose cellular calcium. Diabetics experience glomeral damage and greater sensitivity. 

Thawley DG, Willoughby RA, McSherry BJ. et al. 1977. Toxic interaction among lead, zinc, and cadmium with varying levels of dietary calcium and vitamin D. Environ Res 14 463-475. 

Cadmium is nutritionally non-essential, toxic and a ubiquitous environmental pollutant. It is found in leafy vegetables, grains and cereals, and since it is present in substantial amounts in tobacco leaves, cigarette smokers on a packet a day can easily double their cadmium intake. It has a long biological half-life (17-30 years in man), accumulates in liver and kidneys and its toxicity involves principally kidney and bone (Goyer, 1997).While Cd interferes primarily with calcium, it also interacts with zinc and can induce the synthesis of metallothionein. Cadmium bound to metallothionein in liver or kidney is thought to be non-toxic, but cadmium in plasma... 

Lucu, C. and Obersnel, V. (1996). Cadmium influx across isolated Carcinus gill epithelium. Interaction of lanthanum and calcium with cadmium influxes, J. Comp. Physiol. B., 166, 184-189. 

J. Benters, U. Flogel, T. Schafer, D. Leibfritz, S. Hechtenberg, D. Beyersmann, Study of the interactions of cadmium and zinc ions with cellular calcium homoeostasis using F-19-NMR spectroscopy, Biochem. J. 322 (1997) 793-799. 

Christoffersen, J., Christoffersen, M. R., Larsen, R., Rostrup, E., Tingsgaard, P., Andersen, O. Grandjean, P. 1988. Interaction of cadmium ions with calcium hydroxyapatite crystals a possible mechanism contributing to the pathogenesis of cadmium-induced bone diseases. Calcified Tissue International, 42, 331 -339. 

Moszynski R, Lach G, Jaszunski M, Bussery-Honvault B (2003) Longrange relativistic interactions in the Cowan-Griffin approximation and their QED retardation Application to helium, calcium, and cadmium dimers. Phys Rev A 68 052706... 

---