Renal Lesions in Experimental Cadmium Poisoning

Bonnell, J.A.; Ross, J. H.; King, E.

doi:10.1136/oem.17.1.69

Cited by 29 publications

(12 citation statements)

References 9 publications

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“…Such a time lag was not pointed out in previous papers (Axelsson and Piscator, 1966a;Bonnell et al, 1960;Yoshikawa, 1979), in which Cd accumulation was shown to reach its maximum or plateau level in both liver and kidney at a time after long-term Cd exposure. Nevertheless,.the time lag indicates that the second sharp increase in urinary excretion of Cd in stage III is related to the decline of hepatic Cd.…”

Section: Discussionmentioning

confidence: 51%

Cadmium metabolism and toxicity in rats after long‐term subcutaneous administration

Suzuki¹

1980

Journal of Toxicology and Environmental Health

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Male Sprague-Dawley rats were given sc injections of Cd at 0.5 mg/kg body weight, 6 d/wk, for 22 wk. Concentrations in the liver, kidney, spleen, heart, testis, and blood were determined every week for 8 wk and at the end of 10, 12, 15, and 22 wk. Daily excretion of Cd and total protein in urine were determined every week in another series of rats given the same dose for up to 25 wk. Hepatic and renal Cd increased linearly for the first several weeks of Cd injection. The Cd concentration in the kidney leveled off at 156 microgram/g wet tissue after 7 wk, whereas hepatic Cd continued to increase for a few more weeks, reached its maximum level (330 microgram/g) at 10 wk, and then declined. Blood Cd showed a steady increase expressed by a logarithmic curve for the first several weeks and a rapid rise in response to the decline of hepatic Cd. Urinary excretion of Cd increased linearly but slightly for several weeks from the beginning of injections. In this period daily excretion of Cd remained less than 1% of the daily Cd dose. From 6 wk the Cd excretion increased rapidly and reached a plateau of about 10 microgram/d (several percent of the daily dose) with a simultaneous increase in urinary excretion of total protein. Urinary excretion of Cd showed a second sharp increase after 10 wk and reached a higher plateau level of 95 microgram/d (about 63% of the daily dose). From these findings the response of the exposed animals could be divided into three stages. The first stage was characterized by a steady increase in hepatic and renal Cd and low-level excretion in the urine. This stage was regarded as a latent period of Cd poisoning. The second stage, which developed between 5 and 7 wk, was characterized by leveling off of Cd accumulation in the kidney and increased excretion of Cd and total protein in the urine. This was an initial toxic stage represented by renal lesions. The third stage was characterized by the second sharp increase in urinary Cd excretion and an elevated level of blood Cd after 10 wk. These responses were related to a decrease in the hepatic capacity for Cd retention as a result of toxic effects of Cd on the liver.

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Section: Discussionmentioning

confidence: 51%

Cadmium metabolism and toxicity in rats after long‐term subcutaneous administration

Suzuki¹

1980

Journal of Toxicology and Environmental Health

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“…The continuous exposure resulted in a plateau and a subsequent decline (Axelsson and Piscator 1966). In rat, a linear increase was observed until the equilibrium states of 200-300 and 350 μg/g wet tissue weight in kidney and liver, respectively, after a 0.75 mg/kg intraperitoneal injection of Cd silver nitrate (Bonnell et al 1960). Similar correlations and regressions between Cd contents in liver and kidney were observed in wildlife such as fulmar (Flumarus glacialis ) and southern fulmar (Flumarus glacialoides) (Norheim 1987) oystercatcher (Haematopus ostralegus) and great skua (Chatharacta skua) (Hutton 1981), and ducks (Mochizuki et al 2002).…”

Section: Discussionmentioning

confidence: 89%

A new index for evaluation of cadmium pollution in birds and mammals

Mochizuki

Mori

Hondo

et al. 2007

Environ Monit Assess

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The degree of cadmium (Cd) contamination in wildlife is often used as an indicator in the environmental monitoring of Cd poisoning. However, previous studies have not clarified the correlation between levels in wildlife and levels in the environment by comparing levels among different species of animals; therefore, assessing the level of pollution in this manner is not considered a reliably accurate indicator of levels in the environment. The aim of this study was to establish a new indicator for the non-polluted warm-blooded animals, one that is not species-dependent, which will facilitate using different species for Cd monitoring. First, the previous publications regarding Cd contents in wildlife, 27 reports in which Cd contents were represented as arithmetic means and described for both kidney and liver were selected. A regression line (CSRL) between Cd contents of kidney and that of liver was obtained in a high correlation coefficient (R (2) = 0.943, P < 0.01). The mean values from land and waterfowl, terrestrial mammals, seabirds, marine mammals, and non-polluted humans were located on the line and aligned in order. CSRL might allow an accurate determination of whether an animal is polluted by Cd. CSRL was confirmed using well-established and widely recognized pollution models such as Itai-itai patients and Cd-exposed experimental animals. The Cd contents from these models were located in different positions relative to CSRL depending on the level of contamination. Thus, this new indicator determining the Cd-pollution status of animals would be useful for environmental monitoring.

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“…In Cd-exposed people, the chronic toxicity such as renal dysfunction will appear only after a long lag period of several years, and when a critical concentration of renal Cd is reached (8,9). It is known that there is a gradual mobilization of Cd from liver to kidney and the major critical organ in chronic Cd toxicity is the kidney (10)(11)(12). Therefore, it is important to consider all the factors involved in the renal deposition of Cd to develop an effective chelation therapy for Cd and to prevent the Cd induced renal disease.…”

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confidence: 99%

Chelation of cadmium without increased renal cadmium deposition.

Cherian¹

1984

Environ Health Perspect

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Cadmium (Cd) is mainly accumulated in liver and kidney bound to metallothionein (MT) and excreted very slowly from the body. In chronic exposure, Cd is gradually transported from liver to kidney; the renal toxic effects appear when renal Cd concentration exceeds the critical concentration. In order to prevent the Cd-induced renal disease, it is important to control the movement of Cd to the kidney and its renal deposition. However, the chelation of Cd from liver is difficult because of the high affinity of intracellular MT for Cd. A number of chelating agents containing both carboxyl and thiol groups were able to mobilize and excrete Cd more easily in a short time (1/2 hr) after Cd exposure than longer times (24 hr), after MT synthesis. The renal deposition of Cd increased on BAL (2,3-dimercaptopropanol) treatment a short time (1/2 hr) after Cd exposure. However, it was observed that if BAL was administered 24 hr after Cd exposure, it could mobilize Cd from hepatic MT and increase the biliary excretion of Cd without any increase in renal Cd concentration. Studies using a number of structurally related thiols (mono-, di-and trithiols) showed that the major structural requirement for in vivo chelation of Cd from intracellular MT were the vicinal thiol groups on an aliphatic chain, and lipophilicity. BAL was the most effective of all the compounds studied and it did not mobilize Cd to the kidney, when most of the intracellular Cd was bound to MT. Furthermore, a delayed treatment with BAL or DTPA (diethylenetriamine pentaacetic acid) after synthesis of MT resulted in an increase in fecal or urinary excretion of Cd in rat model experiment. The injection of DTPA in combination with BAL was more effective in decreasing the concentration of Cd and MT in liver and kidney from rats chronically exposed to Cd than injection of BAL alone. Since DTPA cannot enter the cell, it may be acting extracellularly in removing the Cd. The results of these studies suggest that the specific intracellular binding of Cd to MT is an important factor in protecing kidney, the critical organ, in the effective chelation of Cd by BAL.The development of an effective chelation therapy for cadmium (Cd) has been extremely difficult because of the special features in the pharmacokinetics and toxicity of Cd compounds. Unlike other metals, Cd has an unusually long biological half-time in human and is excreted very slowly from the body (1). After absorption from the respiratory and gastrointestinal tracts, Cd is mainly accumulated in liver and kidney bound to metallothionein (MT), a low molecular weight sulfur-rich intracellular protein (2,3). The low excretion of Cd from the body may be closely related to its specific intracellular binding to MT. Although acute and chronic Cd poisonings in humans are not common, there are isolated cases of chronic Cd poisoning in workmen and people liv-

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Renal Lesions in Experimental Cadmium Poisoning

Cited by 29 publications

References 9 publications

Cadmium metabolism and toxicity in rats after long‐term subcutaneous administration

Cadmium metabolism and toxicity in rats after long‐term subcutaneous administration

A new index for evaluation of cadmium pollution in birds and mammals

Chelation of cadmium without increased renal cadmium deposition.

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