In order to study the critical concentration of cadmium (Cd) in acute renal dysfunction following Cd, male mice were injected IV with Cd complexed with cysteine. The critical concentration was 10 micrograms Cd/g wet weight in whole kidney and it was the same as that for Cd-thionein (Cd-Th), which may suggest that the toxicity of Cd-Th is due to Cd ions liberated from Cd-Th in the kidneys. Renal Cd concentration was at first higher than the critical concentration, but decreased to the critical concentration by 24 h after administration. As an index for renal dysfunction, the uptake of p-aminohippurate (PAH) by renal cortical slices in vitro was sensitive, and showed the different time-course from those of urinary protein and glucose levels. The results suggest the usefulness of PAH uptake as an index. Incidental to the renal dysfunction, renal calcium levels exhibited a marked increase.

1985-10-01·Toxicology3区 · 医学

Cadmium found in non-soluble fraction of kidney homogenates and its relation to renal dysfunction after cadmium-cysteine administration

3区 · 医学

Article

作者: Kazuo T. Suzuki ; Yukio Saito ; Tamio Maitani

The critical concentration of cadmium (Cd) in the kidney after acute administration of Cd-cysteine (Cys) is 10 micrograms/g wet wt in whole kidney and is equal to that following Cd-thionein (Th) injection. This fact suggests that the nephrotoxicity of Cd-Th may be due to the Cd ions liberated from Cd-Th. To clarify the mechanism of the nephrotoxicity, the subcellular distribution of Cd injected as Cd-Cys was determined between supernatant and sediment fractions. Renal Cd level observed at 4 h increased with dose, but the Cd concentration in the supernatant fraction was kept almost constant at higher doses. Renal dysfunction measured by urinary protein and glucose levels was seen at the higher doses. This suggested that Cd in the sediment fraction of the kidney homogenates may be the ultimate cause for the nephrotoxicity of Cd-Cys. The sedimental Cd was eliminated from the kidney by 24 h. Much of the Cd found in the supernatant fraction was bound to high-molecular-weight proteins (HMWP) at 4 h, and almost all Cd ions were found to be bound to metallothionein at 24 h. Therefore, the HMWP-bound Cd in the supernatant fraction also may be a cause for the renal dysfunction. It is concluded that in addition to the HMWP-bound Cd in the supernatant fraction, CD distribution into the sediment fraction should be considered as a factor in causing nephrotoxicity after Cd-Cys and possibly Cd-Th administration.

1984-06-01·Toxicology and Applied Pharmacology3区 · 医学

Distribution of cadmium after oral administration of cadmium-thionein to mice

3区 · 医学

Article

作者: Michael P. Waalkes ; Curtis D. Klaassen ; Tamio Maitani

Distribution of Cd was compared after oral administration of either Cd ions or Cd-thionein (Cd-TH). Mice received 0.5 mg Cd/kg, po as CdCl2 in saline, CdCl2 in control rat liver homogenate, Cd-TH in saline, Cd-TH in liver homogenate, or liver homogenate from Cd-treated rats. In all cases, 85-90% of the Cd dose was present in feces within 24 hr. However, in groups receiving CdCl2, more Cd was found in feces on Days 2 and 3 in comparison to those receiving Cd-TH. All treatments resulted in lower levels of Cd in liver than in kidney. In addition, tissue levels indicate that less Cd was absorbed when rats received Cd-TH in saline than CdCl2 in saline. Cd-TH added to liver homogenate or liver homogenate containing Cd-TH increased the absorption of Cd resulting in renal Cd levels similar to those in mice receiving CdCl2 in saline. The kidney/liver Cd concentration ratio (9) was the same for Cd-TH in all three media. Although Cd-TH gave much higher kidney/liver Cd ratios than CdCl2 (9 vs 2), renal Cd concentrations were the same or lower than after CdCl2 treatments. Results indicate that the high kidney/liver Cd ratio after Cd-TH treatment versus CdCl2 is due to lower concentrations of Cd in liver rather than marked increases in renal Cd levels. Heating of Cd-TH did not result in lower amounts of Cd in kidney. While the chemical form of Cd administered affects the absorption and distribution of Cd, the amount of Cd reaching the kidney after Cd-TH administration is similar to that after CdCl2 administration.

100 项与 CAR-TH(Jiangsu Pacific Meinuoke Bio Pharmaceutical) 相关的药物交易

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