Different binding forms of cadmium--implications for distribution and toxicity.
Our present understanding of mechanisms for induction of renal tubular damage by cadmium is summarized in Fig 1: Cadmium is taken up from various exposure routes into plasma where it is initially bound to albumin. Such cadmium is mainly taken up by the liver where it induces the synthesis of metallothionein, which is mainly kept intracellularly, but a small proportion escapes into blood plasma. Cadmium bound to metallothionein in plasma is quickly transported to the kidney tubule by glomerular filtration and subsequent uptake by pinocytosis into renal lysosomes. Uptake of cadmium bound to low mol. wt protein from hemolyzed blood cells may also contribute to cadmium accumulation in the renal tubule. Cadmium is released from metallothionein in the renal lysosomes, where proteins are catabolized. Non-metallothionein bound cadmium may then interact with sensitive sites in the renal cell and cause renal tubular damage. There is an internal synthesis of metallothionein in the renal cells and a balance is thus formed between metallothionein bound cadmium and non-metallothionein bound cadmium. Only in such situations when non-metallothionein bound cadmium reaches a sufficient concentration does the renal damage appear. This scheme has been based mainly on observations in animals and cellular systems. It is probable that similar conditions occur in humans; however, the amount of human evidence available to quantify the different pathways is limited. Nevertheless, based on several assumptions, a quantitative model has been designed for humans concerning relationships between exposure and development of renal damage. Available data have been summarized in two chapters of a recent publication (Nordberg et al 1985, Kjellström and Nordberg 1985). Much more data on humans would be desirable to make this kind of extrapolation with confidence.
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D000388:Air / Q000032:analysis; D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D002104:Cadmium / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism
D002352:Carrier Proteins; D002104:Cadmium; D008668:Metallothionein