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In the present study, the role of endothelin-1 (ET-1) on alterations of hepatic and renal metallothionein (MT) and trace metals (Zn, Cu, and Fe) were investigated in streptozotocin (STZ)-induced diabetic rats. Diabetic rats, age- and sex-matched controls, as well as control and diabetic animals on a dual ET A /ET B receptor blocker, bosentan, were investigated after 6 months of follow-up. MT was measured by cadmium-heme assay. Metals were measured by atomic absorption spectrometer. ET-1 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Hepatic and renal ET-1 mRNA was increased in diabetic rats as compared to control rats, along with an increase in both hepatic and renal MT proteins. The increased hepatic MT protein level was associated with decreases in hepatic Cu and Fe, whereas increased renal MT was associated with increases in renal Cu and Fe accumulation. Zn levels were unaltered in both organs in diabetic rats. Bosentan treatment partially prevented the increase in MT levels in both liver and kidney, along with reduced serum creatinine and increased urinary creatinine levels. Further bosentan treatment corrected the increased Cu and Fe levels in the kidney in diabetic rats, but reduced hepatic Cu and Fe levels. No significant effects of bosentan treatment on nondiabetic rats were observed. The data suggest that the possible effects of ET antagonism in diabetes may be mediated via changes in MT and trace metals. [ABSTRACT FROM AUTHOR]

Body retention and tissue distribution of Cd from oral 109 CdCl 2 and 109 Cd‐metallothionein were studied in C57BL/6J mice given identical doses (60 μg Cd and 2 μCi 109 Cd). Measurement of 109 Cd radioactivity in mice showed identical absorption but differences in tissue distribution of Cd from the two forms. A significantly greater deposition of Cd was observed in the kidney of mice fed Cd‐metallothionein than in the CdCl 2 group where a major portion of Cd was deposited in the liver. Most of the radioactive Cd in the renal and hepatic tissues and in the duodenum was bound to metaltothionein 24 h after oral Cd‐metallothionein, whereas only 30 and 38% of the cadmium in liver and kidney supernatants, respectively, were bound to metallothionein after oral CdCI 2 . These results suggest that the dietary form of Cd may influence the renal deposition of Cd. [ABSTRACT FROM PUBLISHER]

Intravenous injection of 109Cd‐labeled CdCI2 (I mg/kg) to control rats and rats that had been injected with CdCI2 (0.25 mg/kg) 24 hr earlier showed that there was a decrease in the biliary excretion of 109Cd in the latter group. The 24 hr pretreatment with CdCI2 resulted in induced synthesis of metallothionein in rat liver and kidney. The binding of cadmium to liver tissue was increased and the renal accumulation of cadmium was unaltered on cadmium pretreatment. Rat liver metallothionein was isolated from rats injected repeatedly with CdCl2 Intravenous injection of cadmium‐bound metallothionein gave a different distribution of cadmium in the tissues and biological fluids as compared to injection of CdCl2. A major percentage of cadmium was deposited in the kidney with urinary excretion after injection of rat cadmium‐metallothionein to control rats. The biliary excretion of cadmium after cadmium‐metallothionein injection was minimal. About 90% of cadmium in the kidney cortex and urine could be recovered as cadmium‐thionein in sephadex gel filtration, 3 hr after cadmium‐thionein injection. [ABSTRACT FROM PUBLISHER]

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 CdCl1. 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. [ABSTRACT FROM PUBLISHER]

In protecting the body against the noxious effects of dietary cadmium ions, cadmium is bound to metallothionein in the proximal intestine, and subsequently excreted into the lumen with desquamation of the epithelium. The purpose of this study was to determine the extent to which cadmium in the form of intestinal cadmium‐thionein is absorbed from the intestinal lumen and to appraise the toxicity of cadmium‐thionein on the intestinal mucosa. With open‐ended duodenal perfusion, equivalent amounts of cadmium administered as CdCl2 or cadmium‐thionein entered the mucosa, but significantly less cadmium from the perfusate of cadmium‐thionein passed into the body. Exposure of the mucosa to CdCl2 for 1 hr led to minor abnormalities in the form of broadening of villi with pseudostratification of epithelium, and swelling of mitochondria, whereas cadmium‐thionein produced extensive necrosis of absorptive cells. The results suggest that cadmium‐thionein may play a paradoxical role, providing protection against the cadmium ion in the intracellular milieu, but promoting cadmium toxicity when it is present in sufficient amounts in the lumen of the intestine. [ABSTRACT FROM PUBLISHER]

Describes the distribution of mercury in red blood cells and plasma. Excretion of mercury in human subjects after inhalation of vapor; Correlation between urinary excretion and plasma radioactivity of mercury; Use of blood mercury levels as an index of mercury exposure; Absence of reliable index for mercury concentration in the brain.

Examines the metallothionein (MT) levels in liver and kidney of Canadians as a potential indicator of environmental exposure to cadmium (Cd). Hypothesis of MT as a regulatory and detoxifying intracellular metalloprotein; Correlation between MT and Cd and zinc (Zn) levels in kidney; Linear relationship between MT and Zn in the liver.

Examines the effect of mixture of stable and radioactive mercury vapor on human subjects. Analysis on the distribution of inhaled mercury to the different organs; Impact of mercury vapor on the lungs; Measurement of the body parts for mercury clearance through external gamma counting.