Experimental localization of intestinal uptake sites for metals (Cd, Hg, Zn, Se) in vivo in mice.

Andersen, Ole; Nielsen, Jesper Bo; Sørensen, Jens Ahm; Scherrebeck, Leif

doi:10.1289/ehp.94102s3199

Cited by 27 publications

(9 citation statements)

References 40 publications

(35 reference statements)

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“…The absorption of these metals occurs predominantly in the upper intestine and can be divided into three steps: (1) a membrane transporter facilitates the transport of the metal at the brush border membrane, (2) serosal transfer to the basolateral side, and (3) basolateral transfer of the metal to the plasma. Early animal studies showed that maximal absorption of Pb15,16 and Cd17,18 also occurs in the upper intestine by a carrier‐mediated process 19,20…”

Section: Intestinal Transport Of Fe CD and Pbmentioning

confidence: 99%

Divalent Metal Transporter 1 in Lead and Cadmium Transport

Bressler

Olivi

Cheong

et al. 2004

Annals of the New York Academy of Sciences

208

105

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The effect of exposure to cadmium (Cd) and lead (Pb) on human health has been recognized for many years and recent information suggests that minimal exposure levels are themselves too high. Common scenarios for Pb exposure include occupational, residential, and/or behavioral (hand-to-mouth activity) settings. The main source of Cd exposure for nonsmokers is dietary, through plants or animals that accumulate the metal. Specific cellular importers for Pb and Cd are unlikely as these metals are nonessential and toxic. Accordingly, in the intestine, the operational mechanism is assumed to be inadvertent uptake through pathways intended for essential nutrients such as iron. Results from experimental and epidemiological studies indicated that diets low in iron (Fe) result in increased absorption of Pb and Cd, suggesting common molecular mechanisms of Cd and Pb transport. Indeed, recent mechanistic studies found that the intestinal transporter for nonheme iron, divalent metal transporter 1 (DMT1), mediates the transport of Pb and Cd. DMT1 is regulated, in part, by dietary iron, and chemical species of Cd and Pb that are transported by DMT1 would be made available through digestion and are also found in plasma. Accordingly, the involvement of DMT1 in metal uptake offers a mechanistic explanation for why an iron-deficient diet is a risk factor for Pb and Cd poisoning. It also suggests that diets rich in iron-containing food could be protective against heavy metal poisoning.

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Section: Intestinal Transport Of Fe CD and Pbmentioning

confidence: 99%

Divalent Metal Transporter 1 in Lead and Cadmium Transport

Bressler

Olivi

Cheong

et al. 2004

Annals of the New York Academy of Sciences

208

105

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“…Understanding of the mechanisms of Cd absorption and circumventing the intestinal barrier is of prime interest. Available literature reports that, following oral exposure, Cd is absorbed in mammals preferentially in the duodenum and proximal jejunum [ 8 ]. After absorption Cd first reaches the liver.…”

Section: Introductionmentioning

confidence: 99%

Impact Assessment of Cadmium Toxicity and Its Bioavailability in Human Cell Lines (Caco-2 and HL-7702)

Aziz

Rafiq

Yang

et al. 2014

BioMed Research International

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Cadmium (Cd) is a widespread environmental toxic contaminant, which causes serious health-related problems. In this study, human intestinal cell line (Caco-2 cells) and normal human liver cell line (HL-7702 cells) were used to investigate the toxicity and bioavailability of Cd to both cell lines and to validate these cell lines as in vitro models for studying Cd accumulation and toxicity in human intestine and liver. Results showed that Cd uptake by both cell lines increased in a dose-dependent manner and its uptake by Caco-2 cells (720.15 µg mg−1 cell protein) was significantly higher than HL-7702 cells (229.01 µg mg−1 cell protein) at 10 mg L−1. A time- and dose-dependent effect of Cd on cytotoxicity assays (LDH release, MTT assay) was observed in both Cd-treated cell lines. The activities of antioxidant enzymes and differentiation markers (SOD, GPX, and AKP) of the HL-7702 cells were higher than those of Caco-2 cells, although both of them decreased significantly with raising Cd levels. The results from the present study indicate that Cd above a certain level inhibits cellular antioxidant activities and HL-7702 cells are more sensitive to Cd exposure than Caco-2 cells. However, Cd concentrations <0.5 mg L−1 pose no toxic effects on both cell lines.

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“…Intestinal Cd absorption may occur either by paracellular or transcellular routes, or both. In vivo and in situ studies have shown a substantial accumulation of Cd in the intestinal tissue following oral exposure and luminal perfusion, respectively (Hoadley and Cousins, 1985;Lehman and Klaassen, 1986;Foulkes and Mc-Mullen, 1987;Andersen et al, 1994). Also, uptake experiments performed on brush-border membrane vesicles isolated from the rat and the pig small intestine have clearly demonstrated that Cd is taken up by intestinal cells (Bevan and Foulkes, 1989;Tacnet et al, 1990); thus transcellular routes seem to be involved in Cd absorption.…”

mentioning

confidence: 99%

Evidence for an intracellular barrier to cadmium transport through caco-2 cell monolayers

et al. 1999

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109Cd transport was studied in the highly differentiated TC7 clone of the enterocytic-like Caco-2 cells grown on filters. Accumulation curves for 0.3 microM 109Cd over 12 h from the apical (AP) or the basal (BL) sides revealed a three-step mechanism involving: 1) a zero-time accumulation Ao; 2) a fast process Af(t1/2 < or = 10 min); and 3) a slow process of uptake As (5 h < or = t1/2 < or = 10 h) responsible for the major cellular levels of 109Cd. The relative contribution of adsorption to total accumulation is greater for short exposure times (< or = 35%), but is no longer significant after the exposure times needed to reach equilibrium. Transepithelial transport was less than 4% of the cellular level at 12 h. A negligible but specific binding onto the BL surface of the filters was characterized. Saturable systems of accumulation with comparable affinities (Km = 2.5+/-0.5 and 5.4+/-0.4 microM) but distinct capacities (Vmax = 8.9+/-1.2 and 312+/-22 pmol/min/mg protein) were identified at the AP and BL cell membranes, respectively. Efflux studies revealed that Cd accumulation is only partially reversible, with an exclusive metal release at the same side. A 2-h exposure on both sides simultaneously failed to demonstrate any competition for cellular accumulation: uptake was additive relative to AP and BL uptake values. These data suggest that Af leads to an accumulation of loosely bound Cd, whereas As represents irreversible intracellular binding processes. We conclude that Cd transport occurs exclusively by a transcellular route and that saturation of the intracellular high-capacity binding sites is the rate-limiting step in Cd absorption.

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Experimental localization of intestinal uptake sites for metals (Cd, Hg, Zn, Se) in vivo in mice.

Cited by 27 publications

References 40 publications

Divalent Metal Transporter 1 in Lead and Cadmium Transport

Divalent Metal Transporter 1 in Lead and Cadmium Transport

Impact Assessment of Cadmium Toxicity and Its Bioavailability in Human Cell Lines (Caco-2 and HL-7702)

Evidence for an intracellular barrier to cadmium transport through caco-2 cell monolayers

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