Studies on poisonous metals. V. Excretion of cadmium through bile and gastrointestinal mucosa and effect of chelating agents on its excretion in cadmium-pretreated rats.

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Abstract
The excretion of cadmium through the bile and gastrointestinal mucosa after the intraperitoneal administration of cadmium chloride and the effect of the chelating agents such as citric acid, D-cysteine, and DL-penicillamine on its excretion were studied in rats pretreated with cadmium. Cadmium pretreatment caused an appreciable decrease in the biliary excretion of subsequently administered cadmium and had no effect on the excretion of the metal through the gastrointestinal mucosa. The chelating agents used had no stimulatory effect on the biliary excretion of cadmium and scarcely affected the excretion of the metal through the gastrointestinal mucosa in the pretreated rats. Moreover, a mechanism of the effect of cadmium pretreatment on the excretion of cadmium through the bile in rats was investigated. From findings relating to the contents of cadmium and zinc in the liver and kidney, the biliary and urinary excretion of both metals, and the binding characteristics of both metals to different proteins in the supernatant of liver, it was suggested that a part of subsequently administered cadmium replaced the zinc bound to metallothionein synthesized in the liver by the pretreatment, resulting in a decrease in the biliary excretion of cadmium and no stimulatory effect of the chelating agents on its excretion.