Multispecies retention parameters for cadmium

Thomas, Robert G.; Wilson, Julie; London, J.E.

doi:10.1016/0013-9351(80)90105-x

Cited by 11 publications

(6 citation statements)

References 33 publications

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“…We tried to evaluate the effect of age on cadmium retention in the kidney from seven different experiments not specially designed for this purpose. However, our data are in general agreement with the results of more detailed studies on cadmium retention and distribution recently published by several authors (11)(12)(13)(14)(15). A detailed comparison of the results is very difficult to make because of different experimental conditions (time, frequency, dose, route of cadmium administration, etc.)…”

Section: Discussionsupporting

confidence: 90%

Effect of age and diet on renal cadmium retention in rats.

Kostial¹

1984

Environ Health Perspect

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The results of our previous and recent work on cadmium metabolism in relation to age and diet are presented. Experiments were performed on albino rats aged 1-26 weeks. In some experiments rats were given different foods (milk, meat, bread) instead of standard rat diet. Some animals received trisodium calcium salt of diethylenetriaminepentaacetate (DTPA) intraperitoneally to decrease cadmium retention. Radioactive cadmium (115mCd) was administered orally and intraperitoneally. Whole body (WB), carcass (C) and organ (kidney, liver and brain) retentions were determined 1 and 2 weeks after a single radioisotope administration. The results are expressed as percentages of the administered dose (% D) and as percentages of whole body (% WB) and carcass (% C) radioactivities. After oral administration whole-body cadmium retention was higher in sucklings than in weaned animals, primarily due to increased gut retention. The kidney retention of orally administered cadmium was about 5-7 times higher in sucklings than in older rats. Cadmium distribution (% C) was similar after oral and intraperitoneal administration. In sucklings, kidney retention made a lower fraction of the carcass radioactivity one week after 115mCd administration but reached adult values a week later. Liver retention in sucklings was a slightly lower fraction of the carcass radioactivity than in older rats at both time intervals. Brain retention (% C) was about 10 times higher in sucklings than in older rats throughout the experiment. Preliminary data on the influence of dietary treatments and treatment with DTPA indicate that some treatments which influence cadmium retention also influence cadmium distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 90%

Effect of age and diet on renal cadmium retention in rats.

Kostial¹

1984

Environ Health Perspect

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“…5,45 Even though 90%-95% of ingested Cd remains unabsorbed, 45 Cd exposure is unfortunately cumulative, with an extremely long biological half-life of 10-30 years in humans. 4,46 More than a dozen studies with autopsy tissues have reported that nonoccupationally exposed individuals may accumulate a significant amount of Cd in the kidney (e.g., 0.62-61.3 mg/g tissue, or w5.5-545 mM). 5 In our animal studies, both acute CdMT treatment and 10 weeks of 10 ppm Cd exposure via drinking water led to mouse renal Cd accumulation (from w5.0 to w15.6 mg/g tissue; Supplementary Figure S12) in the concentration range of those in human renal tissues.…”

Section: Discussionmentioning

confidence: 99%

Cadmium exposure enhances organic cation transporter 2 trafficking to the kidney membrane and exacerbates cisplatin nephrotoxicity

Yang

Tang

Guo

et al. 2020

Kidney International

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Renal accumulation and exposure of cadmium originating from pollution in agricultural land and the prevalence of cigarette smoking remains an unneglectable human health concern. Whereas cadmium exposure has been correlated with increased incidence of a variety of kidney diseases, little is known pertaining to its effect on renal drug disposition and response in patients. Here, we report that cadmium exposure significantly increased the activity of organic cation transporter 2 (OCT2), a critical renal drug transporter recommended in United States Federal Drug Administration guidance for assessment during drug development. Cadmium enhanced OCT2 trafficking to the cell membrane both in vitro and in vivo. Mechanistically cadmium-mediated OCT2 translocation was found to involve protein-protein interaction between serine/ threonine-protein kinase AKT2, calcium/calmodulin and the AKT substrate AS160 in in vitro cellular studies. The formed protein complex could selectively facilitate phosphorylation of AKT2 at T309, which induced translocation of OCT2 to the plasma membrane. Moreover, cadmium exposure markedly exacerbated nephrotoxicity induced by cisplatin, an OCT2 substrate, by increasing its accumulation in the mouse kidney. Consistently, there was a significant correlation between plasma cadmium level and alteration of renal function in cervical cancer patients who underwent chemotherapy with cisplatin. Thus, our studies suggest that membrane transporter distribution induced by cadmium exposure is a previously unrecognized factor for the broad variation in renal drug disposition and response.

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“…Other tissues are affected (e.g. bone, haemetopoietic and cardiovascular systems) although the critical organ is the kidney (Thomas, Wilson & Londong, 1980). 'Itai Itai byo' This translates literally to 'ouch ouch disease' and cadmium was established as an aetiologic factor in 1968 in the Toyoma Prefecture in Japan (Tsuchiya, 1969).…”

Section: Chronic Poisoningmentioning

confidence: 98%