No abstract

No abstract

No abstract

No abstract

Biliary excretion of cadmium was studied in rats after intravenous injection of different doses of cadmium chloride (0.1-2 mg Cd/kg). The rate of bile flow was not affected by cadmium injection and cadmium was excreted into bile during the first 2 hr after injection. The biliary excretion of cadmium increased with increasing dose of CdCl2. Cumulative biliary excretion of cadmium for 5 hr was 0.065% of the administered dose for groups injected with 0.1 mg Cd/kg as compared to 16.9% of the administered dose for 2 mg Cd/kg. During the 5 hr experimental period, most of the cadmium in liver cytosol was bound to high-molecular-weight proteins and less than 10% was bound to the metallothionein fraction. The biliary cadmium was recovered as a low-molecular-weight compound (less than 4,000) in experiments with various doses of cadmium and no cadmium was attached to high-molecular-weight proteins or metallothionein in the bile. The low-molecular-weight cadmium complex in bile was partially characterized as Cd-glutathione by thin-layer chromatography and amino acid analysis.

These results suggest a relationship between absence of MT and appearance of APPC in human liver tumours, especially in metastatic adenocarcinomas.

The effects of changes in sulfur-containing intracellular ligands on biliary excretion of cadmium were studied in rats. Injection of zinc or copper salts 24 h before intravenous injection of 109CdCl2 (1 mg/kg Cd) decreased biliary excretion of Cd. Pretreatment with cysteine (25 mg/kg) had a similar effect. Depletion of intracellular thiol by injection of diethylmaleate had little effect. The effect of chelating agents on the pharmacokinetics of Cd depended on time of administration of the agents after exposure to Cd. When chelating agents were administered 1/2 h after Cd injection (before the synthesis of metallothionein), the thiol-containing agents (2,3-dimercapto-1-propanol (BAL), DL-penicillamine, N-acetylpenicillamine, and dithioerythritol) increased the biliary excretion of Cd, while the carboxyl-containing ones (EDTA and nitrilotriacetate) increased the urinary excretion of Cd. BAL was the most effective chelating agent, but there was also an increase in the renal concentration of Cd. However, when these chelating agents were administered 24 h after Cd injection (after the synthesis of metallothionein), only BAL increased the biliary excretion of Cd. Renal and hepatic Cd concentrations decreased concurrently after BAL treatment.

In the general population, food constitutes the major environmental source of cadmium (Cd) in nonsmokers. It is established that leafy vegetables, roots, and grains (wheat or rice) can accumulate relatively high amounts of Cd from the soil. Beef liver and kidney and shellfish are also major dietary sources of Cd. The daily intake of Cd in various parts of the world is different and depends on both the dietary habits and concentration of Cd in foodstuffs. Because of the long biological half-life of Cd in humans and absence of any specific indicators of its toxicity, the environmental exposure of Cd should be monitored in various countries. Although environmental Cd poisoning is rare, there are isolated reports on excessive exposure to Cd in Japan and Shipham, a zinc-mining town in England. The body retention and toxicity of Cd depends on various factors, such as daily intake, the form of Cd in food, its interactions with essential elements, and nutritional status of the population. Since kidney is considered a critical organ in Cd toxicity, the indicators of renal dysfunction have been widely used for evaluation of Cd poisoning in occupationally exposed people. It is unclear whether similar indicators can be used for monitoring environmental Cd exposure.