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An Experimental Model of Human Absorptive Enterocytes (Caco- 2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden MITF 071018

An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

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Page 1: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess

the Bioavailability of Various MetalsJonas Tallkvist

Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish

University of Agricultural Sciences, Uppsala, Sweden

MITF 071018

Page 2: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Bioavailability

”The fraction of ingested metal that reaches the systemic circulation”

Page 3: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Factors Influencing Bioavailability

• Dose• Age• pH• Gastrointestinal contents• Nutritional status• Disease

Page 4: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Metals Investigated in Caco-2 Cells

V

Co

Fe

Mn

Ca

Cu

Cd

Zn

Ni

Pb

Cr

Mg

Page 5: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Routes of Metal Absorption

Basement membrane

Blood vessel

Mucosal/apical side

Blood/basolateral side

Enterocytes

Active Passive

Page 6: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

The Caco-2 Cell Model

Apical chamber

Basolateral chamber Permeable filter support

Caco-2 cells

Page 7: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Cadmium Absorption

Zalups and Ahmad (2003) Toxcol Appl Pharm, 186, 3

Page 8: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Tallkvist et al., (2001) Tox Lett, 122, 171

Correlation Between DMT1 Expression and Cd Transport in Caco-2 Cells

Page 9: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Summary

The Caco-2 cell model provides a useful tool to assess the bioavailability of metals at various defined experimental conditions.

The Caco-2 cell model offers the possibility to gain insight into molecular mechanisms implicated in the bioavailability of metals.

Page 10: An Experimental Model of Human Absorptive Enterocytes (Caco-2) to Assess the Bioavailability of Various Metals Jonas Tallkvist Department of Biomedical

Thank-You for Your Attention!