State of iron repletion and cadmium tissue accumulation as a function of growth in young rats after oral cadmium exposure.

To check the hypothesis that adequate dietary iron supplementation reduces cadmium retention and cadmium-induced anaemia during fast growth, three different dietary iron concentrations (6 mg/kg = iron-deficient; 55 mg/kg = marginal iron supply; 180 mg/kg = luxurious iron supply) were offered to growing rats. Four groups of rats at different age (44 days approximately = 150 +/- 6 g, 49 days approximately = 180 +/- 3 g, 57 days approximately = 220 +/- 4 g, and 84 days approximately = 295 9 g) received a diet with 55 mg Fe/kg which is a marginal iron-supply during growth. Six animals in each age group were exposed to 10 mg Cd/l as CdCl2 in the drinking water for 1 week; six animals in each age group received no cadmium. In the youngest and oldest groups additional 6 animals were exposed to the same cadmium dose but received an iron-deficient (6 mg Fe/kg) and an iron-adequate diet (180 mg Fe/kg) together with corresponding controls. The state of iron repletion was monitored by the tissue iron content in liver, kidney, and duodenum as well as by the concentrations of haemoglobin, plasma iron and plasma transferrin. The youngest animals showed the highest percent weight increases. Cadmium administration influenced neither growth rates nor food and water intake. At a dietary iron content of 55 mg/kg, iron repletion was negatively correlated to growth while the cadmium content in liver and kidney showed a positive correlation. At fast growth, a dietary iron content of 6 mg/kg lead to iron-deficiency anaemia and high cadmium retention. At all dietary iron concentrations, cadmium retention as well as the cadmium-related reduction in haemoglobin concentration was significantly higher at fast growth. Adequate dietary iron supplementation reduced cadmium retention and cadmium-induced anaemia significantly. Thus, the delicate balance between iron supply and the increased iron demand during growth can be disturbed within one week by a daily cadmium intake as low as 0.7-1.3 mg Cd/kg body weight.

On the capacity of the rat intestine to excrete lithium ions at therapeutic and toxic plasma lithium concentrations.

Lithium (Li) excretion into the intestinal lumen was quantitated in rats in situ by use of a pendular perfusion technique. Male Sprague-Dawley rats were injected daily (7-10 days) i.p. with 1, 3, and 6 mmol LiCl per kg body weight (n = 9-12). Jejunal as well as ileal and colonic segments were perfused with isotonic saline containing 3H-PEG-4000. Perfusate samples were taken after 0, 5, 10, 20, and 60 min. At the highest dose toxic symptoms were observed. At 6 mmol Li per kg the plasma Li concentrations were higher than those linearly extrapolated from the lower-dose groups, which may be due to inappropriate renal excretion. The Li concentration in the perfusate increased linearly over time and was not significantly different between jejunal and colonic segments. The same ratio between the Li concentration in the plasma and in the luminal perfusate was observed in all groups. Intestinal Li excretion is not impaired by high plasma concentrations. The intestinal capacity to excrete Li is considerable: 45 cm of jejunum is able to excrete the intire plasma Li content in 30-40 min, when Li is not resupplemented from intracellular stores. The renal clearance of lithium (Li) decreases when toxic Li plasma concentrations are reached. Therefore, if it were possible to trap Li in the intestinal lumen, this excretion route might be of therapeutic interest in cases of Li intoxication with impaired renal Li-excretion.

Arsenic-copper interaction in the kidney of the rat.

1. The interaction between As and three toxic metals (Cd, Ni and Pb) and Cu (an essential trace metal) in the kidney was investigated in the rat by feeding diets containing various concentrations of As whilst maintaining constant concentrations of the other elements. After 1, 3, 7 and 15 weeks of feeding, metal contents in the renal cortex and medulla, red blood cells and plasma were determined by atomic emission spectrometry (ICP-AES). 2. As accumulated in the whole kidney, whereas Cu accumulated only in the cortex. Accumulation of Cu was found to depend on the feeding period and dietary As concentration. 3. As was also accumulated in red blood cells, where saturation was found at 550 micrograms As g-1 cells. 4. Although Cd was also accumulated in the cortex, its accumulation was independent of the dietary As concentration. Ni and Pb were not detected by ICP-AES. 5. Chromatography of the supernatants from cortical homogenates of control and As-treated rat kidney suggested that Cu accumulated in renal metallothionein (MT). Its accumulation in this fraction was independent of that of Cd, indicating that the As-Cu interaction was not a result of MT induction, but rather that it might result from altered renal handling of Cu with subsequent incorporation into MT.

Metal-metal interactions among dietary toxic and essential trace metals in the rat.

Exposure to toxic and essential metals is thought to be reflected by corresponding metal concentrations in tissues. However, toxic and essential metals may influence each other in regard to their retention in the body. Therefore a basic diet containing four toxic metals (As 7, Cd 9, Ni 13, and Pb 20 ppm) and adequate amounts of essential metals was fed to rats for 2 weeks. Test groups received the basic diet with increasing concentrations of one of the toxic metals (up to 90 ppm As, 180 ppm Cd, 365 ppm Ni, and 394 ppm Pb). As, Cd, Ni, Pb, Cu, Fe, Mn, and Zn were determined by atomic emission spectroscopy in liver, kidney, intestine, brain, muscle, bone, skin, hair, and blood. A linear relationship between diet and tissue concentration is observed for As and Ni in the kidney, for Cd in the liver, and for Pb in the bone. In other tissues saturation was observed. While Cd-Fe interactions were common to most of the tissues, other interactions were detected only in specific tissues, e.g., As-Cu in the kidney, Cd-Zn in the liver, and As-Mn, Cd-Mn, or Ni-Cu in the intestine. Increases of renal Pb and intestinal Cd by dietary Ni, and a decrease in bone As by dietary Pb were the most pronounced interactions between the toxic metals. The results demonstrate that potential target organs for the evaluation of metal exposure need to be carefully analyzed for interfering metal-metal interactions.

Lithotripsy in the common bile duct using ultrasound. Preliminary in vitro experiments.

In patients with an increased surgical risk, common bile duct stones can be removed with the aid of endoscopic papillotomy. Most stones are either passed spontaneously, or can be drawn out with the Dormia basket. Excessively large stones can first be smashed with the mechanical lithotripter. Some 20% of the stones presenting are, however, too hard to be smashed in this way. A technique was accordingly developed for smashing such bile duct stones using ultrasound. A prerequisite for this technique was the development of an acoustic wave guide that would conduct ultrasound energy even when bent. With this procedure, it will soon be possible to destroy bile duct stones in situ.