The isolation of metallothionein and its protective role in cadmium poisoning

Abstract

People that have been subjected to cadmium poisoning show marked calcified tissue and kidney disturbances. In rats fed a cadmium-containing, low-calcium-vitamin D-deficient diet, the major portion of the cadmium accumulated in the liver and kidneys. Despite the fact that only a small amount (2.8 ppm) of cadmium completely inhibits the in vitro enzymic 1-hydroxylation reaction of 25-hydroxycholecalciferol, the in vivo 1-hydroxylation proceeded without appreciable inhibition even in the rats loaded with large amounts of oral cadmium. No light-microscopic morphological changes could be found in the kidneys of cadmium-fed rats. Most of the cadmium that accumulated in the kidneys was in a form bound to the protein, metallothionein, and therefore was not toxic to that organ. On the other hand, only 20% of the cadmium present in bone appears to be protein bound. The data strongly suggest that the protective effect of metallothionein in the kidney is serendipitous when involved in cadmium poisoning and that cadmium ion acts directly on bone rather than by an indirect action through a functional disturbance of the kidney.