Biliary excretion of cadmium in rat. I. Dose‐dependent Biliary excretion and the form of cadmium in the bile

Mg, Cherian; Jj, Vostal

doi:10.1080/15287397709529493

Cited by 90 publications

(29 citation statements)

References 10 publications

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“…Experimental evidence suggests that Cd conjugates of GSH are likely handled in the same manner. Indeed, the findings of Cherian and Vostal (1977) indicate that Cd 2+ is transported out of bile as a conjugate of GSH. Based on these findings and the fact that the duodenal contents are rich in amino acid and peptides, it is reasonable to suggest that a significant fraction of absorbed Cd 2+ is taken up as a conjugate of these ligands by one or more amino acid and/or peptide transporters.…”

Section: Mimicry and Intestinal Transport Of CD 2+mentioning

confidence: 99%

“…Evidence from thin-layer chromatography of bile from CdCl 2 -treated animals indicates that Cd 2+ is transported from the hepatocyte into bile as a GSH S-conjugate (presumably as G-S-Cd-S-G) by a carrier-mediated process (Cherian and Vostal, 1977). Though a specific carrier has not been identified for this transport, MRP2 is a possible candidate.…”

Section: Mimicry and The Hepatic Transport Of CD 2+mentioning

confidence: 99%

“…Various lines of evidence indicate that a fraction of the Cd 2+ that enters into hepatocytes is secreted into the bile, and is subsequently delivered to the duodenum for excretion in the feces (Cherian and Vostal, 1977;Leslie et al, 2001). Evidence from thin-layer chromatography of bile from CdCl 2 -treated animals indicates that Cd 2+ is transported from the hepatocyte into bile as a GSH S-conjugate (presumably as G-S-Cd-S-G) by a carrier-mediated process (Cherian and Vostal, 1977).…”

Section: Mimicry and The Hepatic Transport Of CD 2+mentioning

confidence: 99%

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Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

649

460

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Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

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Section: Mimicry and Intestinal Transport Of CD 2+mentioning

confidence: 99%

Section: Mimicry and The Hepatic Transport Of CD 2+mentioning

confidence: 99%

Section: Mimicry and The Hepatic Transport Of CD 2+mentioning

confidence: 99%

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Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

649

460

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“…Previous studies (16,17) from our laboratory suggested that biliary excretion of Cd may be an important excretory pathway in a single high dose exposure. The dose-dependent increase in biliary excretion of Cd was similar to that of manganese salts (18) but was different from mercury compounds (19).…”

Section: Biliary Excretion Of CD and Involvement Of Mtmentioning

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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“…The liver is the major organ involved in the metabolism and detoxification of Cd 3) . The biliary excretion of Cd is an important excretory pathway and it is related to fecal and urinary excretion 4) . On the other hand, the kidney is also one of the organs damaged by Cd exposure.…”

mentioning

confidence: 99%

Abnormalities in Cadmium Fluoride Kinetics in Serum, Bile, and Urine after Single Intravenous Administration of Toxic Doses to Rats

Dote

Adachi

Yamadori

et al. 2008

Journal of Occupational Health

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Abnormalities in Cadmium FluorideKinetics in Serum, Bile, and Urine after Single Intravenous Administration of Toxic Doses to Rats: Tomotaro DOTE, et al. Department of Hygiene and Public Health, Osaka Medical College-Cadmium fluoride (CdF 2 , CdF for short) is the most lethal and hepatotoxic of all Cd-containing compounds. The toxic effects of CdF appear to depend on its detoxification and elimination. This study was designed to determine the early dynamics of the absorption, systemic distribution, and metabolism of CdF. The kinetics of cadmium and fluoride were investigated in the blood, bile, and urine of rats as a model of accidental occupational exposure to CdF. The serum concentration-time profiles measured after intravenous CdF (1.34, 2.67 or 4.01 mg/ per kg body weight) administration were analyzed by compartmental modeling using the WinNonlin program. Bile and urine were collected for 300 min after the administration. The kinetic profiles indicate that the clearance of Cd was diminished in the 2.67 and 4.01 mg/kg groups, leading to a persistently high serum Cd level. The mean total biliary excretions of Cd in the 2.67 and 4.01 mg/kg groups were significantly higher than that in the 1.34 mg/kg group. The abnormal kinetics of Cd was attributable to severe hepatic injury that diminished the capacity for Cd accumulation. The elimination of serum F was delayed in the 4.01 mg/kg group. The mean urinary F excretion amount was not significantly higher in the 4.01 mg/kg group than in the 2.67 mg/kg group. The abnormal kinetics of F was attributable to nephrotoxicity that diminished its elimination from the kidney. (J Occup Health 2008; 50: 339-347)

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Biliary excretion of cadmium in rat. I. Dose‐dependent Biliary excretion and the form of cadmium in the bile

Cited by 90 publications

References 10 publications

Molecular and ionic mimicry and the transport of toxic metals

Molecular and ionic mimicry and the transport of toxic metals

Chelation of cadmium without increased renal cadmium deposition.

Abnormalities in Cadmium Fluoride Kinetics in Serum, Bile, and Urine after Single Intravenous Administration of Toxic Doses to Rats

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