Comparison of the toxicity and tissue distribution of cadmium in newborn and adult rats after repeated administration

Wong, King-Lit; Cachia, Richard; Klaassen, Curtis D.

doi:10.1016/0041-008x(80)90064-2

Cited by 52 publications

(16 citation statements)

References 22 publications

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“…This supports the conclusions made by several authors that the higher liver metallothionein concentration (18,19) does not influence cadmium distribution (15,20,21). The higher brain retention found in sucklings is in agreement with several previously published results (11,22). Our results also show that sucklings retain a higher fraction of cadmium in other parts of the body since liver and kidney retentions together represent a lower fraction of the body retention in sucklings than in adult rats.…”

Section: Effect Of Various Foods On Cadmium Retention and Distributionsupporting

confidence: 82%

Effect of Age and Diet on Renal Cadmium Retention in Rats

Kostial¹

1984

Environmental Health Perspectives

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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 (ll5mCd) 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 ll5mCd 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. Our results confirm previous findings that sucklings are at a higher risk than adults at the same level of enviroumental exposure to cadmium.

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Section: Effect Of Various Foods On Cadmium Retention and Distributionsupporting

confidence: 82%

Effect of Age and Diet on Renal Cadmium Retention in Rats

Kostial¹

1984

Environmental Health Perspectives

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“…Pretreatment of animals with low doses of Cd (76,77), Zn (76), ethanol (78), diethylmaleate (79), or triterpenoids (80), all of which are known to increase MT, protect against acute Cd-induced lethality and hepatotoxicity. Newborn animals have a high level of hepatic MT and are resistant to Cd-induced hepatotoxicity (81,82). Similarly, MT-I-transgenic mice, which have concentrations of hepatic MT ten-fold higher than that of control mice (83), are resistant to Cd-induced lethality and hepatotoxicity (84).…”

Section: Role Of Metallothionein In Protection Against Metal Toxicitymentioning

confidence: 98%

METALLOTHIONEIN: An Intracellular Protein to Protect Against Cadmium Toxicity

Klaassen

Liu

Choudhuri

1999

Annu. Rev. Pharmacol. Toxicol.

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1,035

738

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Metallothioneins (MT) are low-molecular-weight, cysteine-rich, metal-binding proteins. MT genes are readily induced by various physiologic and toxicologic stimuli. Because the cysteines in MT are absolutely conserved across species, it was suspected that the cysteines are necessary for function and MT is essential for life. In attempts to determine the function(s) of MT, studies have been performed using four different experimental paradigms: (a) animals injected with chemicals known to induce MT; (b) cells adapted to survive and grow in high concentrations of MT-inducing toxicants; (c) cells transfected with the MT gene; and (d) MT-transgenic and MT-null mice. Most often, results from studies using the first three approaches have indicated multiple functions of MT in cell biology: MT (a) is a "storehouse" for zinc, (b) is a free-radical scavenger, and (c) protects against cadmium (Cd) toxicity. However, studies using MT-transgenic and null mice have not strongly supported the first two proposed functions but strongly support its function in protecting against Cd toxicity. Repeated administration of Cd to MT-null mice results in nephrotoxicity at one tenth the dose that produces nephrotoxicity in control mice. Human studies indicate that 7% of the general population have renal dysfunction from Cd exposure. Therefore, if humans did not have MT, "normal" Cd exposure would be nephrotoxic to humans. Thus, it appears that during evolution, the ability of MT to protect against Cd toxicity might have taken a more pivotal role in the maintenance of life processes, as compared with its other proposed functions (i.e. storehouse for zinc and free radical scavenger).

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“…However, cadmium can be shown to be present in the interstitial tissue of the testis (Berlin and Ullberg 1963;Johnson and Sigman 1971;Nordberg 1972) to the extent of 0.1-0.2% of the administered dose, 12-16 h after the last of seven doses (Wong et al 1980). Indeed, it is known to enter the interstitial cells and so may also cause a direct cellular toxic effect (Waalkes and Poirier 1985).…”

Section: Introductionmentioning

confidence: 96%

Studies on the relationship between acute testicular damage and urinary and plasma creatine concentration

Gray¹,

Nicholson²,

Creasy³

et al. 1990

Arch Toxicol

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A single dose of cadmium chloride (3.23 mumol Cd2+/kg) causing acute testicular damage in male rats also caused significant creatinuria and creatinaemia at 48 h after dosing. Doses of cadmium which did not cause testicular necrosis did not cause creatinuria or creatinaemia. Surgical ligation of the pampiniform plexus also caused ischaemic necrosis of the testis and this was followed by significant creatinuria and creatinaemia. However, neither orchidectomy followed by a toxic dose of cadmium, orchidectomy alone nor sham operation caused significant creatinuria or creatinaemia. Cadmium dosing induced a temporary loss of body weight which was less than that caused by food restriction. Food restriction did not cause significant creatinuria but did cause significant creatinaemia. These data suggest that the creatine is derived from the damaged testis and that measurement of urinary creatine may be a useful non-invasive means of detecting acute testicular damage caused by exposure to chemicals or mechanical impairment of blood flow.

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Comparison of the toxicity and tissue distribution of cadmium in newborn and adult rats after repeated administration

Cited by 52 publications

References 22 publications

Effect of Age and Diet on Renal Cadmium Retention in Rats

Effect of Age and Diet on Renal Cadmium Retention in Rats

METALLOTHIONEIN: An Intracellular Protein to Protect Against Cadmium Toxicity

Studies on the relationship between acute testicular damage and urinary and plasma creatine concentration

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