Defense Mechanisms against Cadmium Toxicity

III. Effects of Pretreatment with a Small Oral Dose of Cadmium on Metallothionein Synthesis after a Large Oral Dose of Cadmium in Mice

Abstract

Pretreatment of female mice with a small oral dose of Cd²⁺ (15 mg Cd²⁺/kg) decreased Cd²⁺ uptake by the liver and kidney and increased that by the small intestinal mucosa at 4 or 24 hr after challenge with a large oral dose of Cd²⁺ (100 mg Cd²⁺/kg). By 4 hr after the challenge dose, more Cd²⁺ taken up by the liver was bound to metallothionein (MT) in the Cd²⁺-pretreated mice than the water-pretreated controls (10 ml H2O/kg); but at 24 hr, the amount of Cd²⁺ bound to MT in the liver and kidney were lower in the former than the latter. The amount of Cd²⁺ not bound to MT in the liver at 4 and 24 hr after the challenge dose and that in the kidney at 24 hr were lower in the Cd²⁺-pretreated mice than the water-pretreated controls. These results suggested that the factor directly related to the toxic action of Cd²⁺ was the amount of Cd²⁺ not associated with MT in the liver and other organs. More Cd²⁺ taken up by the small intestinal mucosa at 24 hr after the challenge dose was associated with MT in the Cd²⁺-pretreated mice than the water-pretreated controls. The present study indicates that MT induced in the small intestinal mucosa by pretreatment prevents Cd²⁺ absorption by sequestering subsequently administered Cd²⁺, and Cd²⁺ taken up by the liver and kidney is bound to MT in an inert form, thus the decrease in the amount of Cd²⁺ not bound to MT, giving protection from the acute oral toxicity of the cation. Pretreatment 24 hr prior to the challenge dose was found to be the most effective.