Abstract
This comparative study of the intestinal absorption of four toxic metals (aluminum, manganese, nickel, and lead) carried out in rats using the in situ intestinal perfusion technique was able to measure the partition of each metal between the intestine (intestinal retention), the blood circulation, and target tissues after 1 h. The perfused metal solutions were at concentrations likely to occur during oral intoxication. It was found that aluminum (48 and 64 mM), even as a citrate complex, crossed the brush border with difficulty (0.4% of the perfused amount); about 60% of this was retained in the intestine and the remainder was found in target tissues (about 36%). Conversely, lead (4.8–48 µM) penetrated the intestine more easily (about 35% of the perfused amount), was slightly retained (about 12% of the input), and was soon found in the tissues (about 58% of the input) and to a lesser degree in circulation (about 29%). Within the same concentration range, nickel and manganese showed certain similarities, such as a reduced crossing of the brush border proportional to the increase in the concentration perfused (0.17–9.5 mM). There was similar intestinal retention and absorption (about 80% and 20% of the input, respectively). Manganese crossed the brush border more easily and was diffused more rapidly into tissues. Finally, the addition of equimolar amounts of iron (4.7 mM) produced opposite effects on the absorption of the two elements, inhibiting manganese and showing a trend to increase in nickel absorption. This could be the result of competition between Fe2+ and Mn2+ for the same transcellular transporters and the slight predominance of paracellular mechanism in the event of “Fe2+-Ni2+” association.
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T. H. Ittel, S. Kinzel, A. Ortmanns, et al., Effect of iron status on the intestinal absorption of aluminum: a reappraisal, Kidney Int. 50, 1879–1888 (1996).
A. E. Gomez-Ayala, M. S. Campos, I. Lopez-Aliaga, et al., Effects of source of iron on duodenal absorption of calcium, phosphorus, magnesium, copper and zinc in rats with ferropaenic anaemia, Int. J. Vitam. Nutr. Res. 67(2), 106–114 (1997).
A. E. Gomez-Ayala, F. Lisbona, I. Lopez-Aliaga, et al., The absorption of iron, calcium, phosphorus, magnesium, copper and zinc in the jejunum-ileum of control and iron-deficient rats, Lab. Anim. 32(1), 72–79 (1998).
T. Kuzuya, T. Hasegawa, Y. Ogura, et al., Effect of transmucosal fluid movement on zinc and copper absorption from rat small intestine, Clin. Exp. Pharmacol. 25(6), 412–416 (1998).
G. B. Van Der Voet and F. A. DeWolff, Intestinal absorption of aluminum: effect of sodium and calcium, Arch. Toxicol. 72(2), 110–114 (1998).
E. Tavares, O. Carreras, A. Gomez-Tubio, et al., Effects of folic acid and amino acids supplementation on zinc intestinal absorption in the progeny of ethanol-treated rats, J. Physiol. Biochem. 56(3), 247–256 (2000).
H. Febel, B. Szegedi, and S. Huszar, Absorption of inorganic, trivalent and hexavalent chromium following oral and intrajejunal doses in rats, Acta Vet. Hung. 49(2), 203–209 (2001).
J. E. Gorsky, A. A. Dietz, H. Spencer, et al., Metabolic balance of aluminum studied in six men, Clin. Chem. 25, 1739–1743 (1979).
M. Brahm, Serum-aluminum in nondialyzed chronic uremic patients before and during treatment with aluminum-containing phosphate-binding gels, Clin. Nephrol. 25, 231–235 (1986).
E. Burgess, Aluminum toxicity from oral sucrafalte therapy, Nephron 59, 523–524 (1991).
D. A. Moneret-Vautrin, D. Burnel, D. Lakomski, et al., Allergie alimentaire par hypersensibilité retardée au nickel contaminant d’un Porto, Alim’Inter: le J. Allerg. Aliment. (CICBAA) 7(3), 115–117 (2002).
R. Seux, M. Clement, B. Grall, et al., Etude expérimentale des facteurs qui conditionnent le comportement de l’eau au contact des canalisations qui contiennent du plomb, Tech. Sci. Méthodes 3, 145–151 (1994).
H. Thiriat-Delon, J. Steffan, D. Nicolas, et al., Enquête de dépistage du saturnisme infantile d’origine hydrique dans les Vosges, Santé Publique 3, 263–273 (1994).
R. M. Galvin, Occurrence of metals in water: an overview, Water (SA) 22(1), 7–13 (1996).
Inserm, Plomb dans l’environnement. Quels risques pour la santé? Les Editions INSERM, Paris (1999).
P. Missy, Recherche de nouveaux chélateurs du manganèse en vue de la détoxication de l’organisme, etudes in vivo et in vitro, PhD thesis, Université de Metz, France (2001).
N. Arnich, M. C. Lanhers, L. Cunat, et al., Nickel absorption and distribution from rat small intestine in situ, Biol. Trace Element Res. 74, 141–151 (2000).
L. Cunat, M. C. Lanhers, M. Joyeux, et al., Bioavailability and intestinal absorption of aluminum in rats: effects of aluminum compounds and some dietary constituents, Biol. Trace Element Res. 76, 31–55 (2000).
S. D. Provan and R. Yokel, Aluminum uptake by the in situ rat gut preparation, J. Pharmacol. Exp. Ther. 245, 928–931 (1988).
P. Mushak, Gastro-intestinal absorption of lead in children and adults: overview of biological and biophysico-chemical aspects, Chem. Spec. Bioavailab. 3(314), 87–104 (1991).
P. Slanina, Y. Falkeborn, W. Frech, et al., Aluminum concentrations in the brain and the bone of rats fed citric acid, aluminum citrate or aluminum hydroxyde, Food Chem. Toxicol. 22, 391–397 (1984).
P. Slanina, W. Frech, A. Bernharson, et al., Influence of dietary factors on aluminum absorption and retention in the brain and bone of rats, Acta Pharmacol. Toxicol. 56, 331–336 (1985).
P. O. Ganrot, Metabolism and possible health effects of aluminum, Environ. Health Perspect. 65, 363–441 (1986).
R. A. Yokel and P. J. McNamara, Aluminum toxicokinetics: an updated minireview, Pharmacol. Toxicol. 88, 159–167 (2001).
T. B. Drüeke, Intestinal absorption of aluminum in renal failure, Nephrol. Dial. Transpl. 17, 13–16 (2002).
C. A. Ecelbarger, G. G. McNeil, and J. L. Greger, Tissue aluminum accumulation and toxic consequences in rats chronically fed aluminum with and without citrate, J. Agr. Food Chem. 42, 2220–2224 (1994).
J. Liu, G. F. Nordberg, and W. Frech, Aluminum accumulation in some tissues of rats with compromised kidney function induced by cadmium-metallothioneine, Pharmacol. Toxicol. 78, 289–295 (1996).
P. Hartemann, Réflexion sur la fixation d’une concentration maximale admissible pour le plomb, communication, J. Techn., AGHTM, Mulhouse, France (1995).
O. Sinnaeve, M. Berthier, O. Guillard, et al., Le saturnisme chronique chez l’enfant aujour-d’hui. Une pathologie de la pauvreté et de l’exclusion, Arch. Pédiatr. 6(7), 762–767 (1999).
F. W. Alexander, The uptake and excretion by children of lead and other contaminants, in Environmental Health Aspects of Lead: Proceedings of an International Symposium, D. Barth, A. Bertin, R. Engel, et al., eds., Commission of the European Communities, Luxembourg, pp. 319–331 (1972).
E. E. Ziegler, B. B. Edwards, R. L. Jensen, et al., Absorption and retention of lead by infants, Pediatr. Res. 12, 29–34 (1978).
N. Gruden and M. Stantic, Transfer of lead through the rat’s intestinal wall, Sci. Total Environ. 3, 288–292 (1975).
J. A. Blair, I. P. L. Coleman, and M. E. Hilburn, The transport of the lead cation across the intestinal membrane, J. Physiol. 286, 343–350 (1979).
P. R. Flanagan, D. L. Hamilton, J. Haist, et al., Interrelationships between iron and lead absorption in iron-deficient mice, Gastroenterology 77, 1074–1081 (1979).
B. J. Aungst and H. L. Fung, Kinetic characterization of in vitro lead transport across the rat small intestine, Toxicol. Appl. Pharm. 61, 39–47 (1981).
B. J. Aungst, J. A. Dolce, and H. L. Fung, The effect of dose on the disposition of lead in rats after intravenous and oral administration, Toxicol. Appl. Pharm. 61, 48–57 (1981).
P. J. Bushnell and H. F. DeLuca, The effects of lactose on the absorption and retention of dietary lead, J. Nutr. 113, 365–378 (1983).
H. M. Mÿkkanen and R. H. Wasserman, Gastrointestinal absorption of lead (203Pb) in chicks: influence of lead, calcium and age, J. Nutr. 111, 1757–1765 (1981).
J. C. Barton, Active transport of lead-210 by everted segments of rat duodenum, Am. J. Physiol. 247, 193–198 (1984).
S. J. Henning and L. L. Leeper, Duodenal uptake of lead by suckling and weanling rats, Biol. Neonate 46, 27–35 (1984).
K. A. Hussein, S. B. Coghill, G. Milne, et al., The uptake of lead by small intestine, colon and gallbladder of the guinea pig in vivo, Histochemistry 81, 591–596 (1984).
A. P. Morton, S. Partridge, and J. A. Blair, The intestinal uptake of lead, Chem. Br. 923–927 (1985).
S. J. Henning and L. C. Cooper, Intestinal accumulation of lead salts and milk lead by suckling rats, Proc. Soc. Exp. Biol. Med. 187, 110–116 (1988).
N. Karmakar and G. Jayaraman, Linear diffusion of lead in the intestinal wall: a theorical study, IMA J. Math. Appl. Med. Biol. 5, 33–43 (1988).
G. B. Freeman, J. D. Johnson, J. M. Killinger, et al., Relative bioavailability of lead from mining waste soil in rats, Fundam. Appl. Toxicol. 19(3), 388–398 (1992).
G. B. Freeman, J. A. Dill, J. D. Johnson, et al., Comparative absorption of lead from contaminated soil and lead salts by weanling Fisher 344 rats, Fundam. Appl. Toxicol. 33, 109–119 (1996).
I. Palminger Hallen, S. Jönsson, M. O. Karlsson, et al., Toxicokinetics of lead in lactating and non lactating mice, Toxicol. Appl. Pharmacol. 136, 342–347 (1996).
C. M. Dekaney, E. D. Harris, G. R. Bratton, et al., Lead transport in IEC-6 intestinal epithelial cells, Biol. Trace Element Res. 58(1–2), 13–24 (1997).
G. B. Van Der Voet and F. A. DeWolff, Intestinal absorption of aluminum in rats: effect of intraluminal pH and aluminum concentration, J. Appl. Toxicol. 6, 37–41 (1986).
C. E. Carpenter and M. Ummadi, Iron status alters the adsorption, uptake, and absorption capacities of rat duodenum for ferrous and ferric iron, Nutr. Res. 15(8), 1129–1138 (1995).
L. L. Hardwick, M. R. Jones, R. K. Buddington, et al., Comparison of calcium and magnesium absorption: in vivo and in vitro studies, Am. J. Physiol. 259, G720-G726 (1990).
C. Bellaton, C. Roche, C. Remy, et al., Absorption du calcium, Gastroenterol. Clin. Biol. 16(3), 239–247 (1992).
D. Pansu, C. Duffos, C. Bellaton, et al., Solubility and intestinal transit time limit calcium absorption in rats, J. Nutr. 123(8), 1396–1404 (1993).
M. E. Conrad and J. C. Barton, Factors affecting the absorption and excretion of lead in the rat, Gastroenterology 47, 731–740 (1978).
M. J. Coogan, Analysis of a model to describe lead transport by the small intestine, PhD thesis, University of Aston, Birmingham, UK (1982).
E. Duizer, A. J. Gilde, C. H. M. Versantvoort, et al., Effects of cadmium chloride on the paracellular barrier function of intestinal epithelial cell lines, Toxicol. Appl. Pharm. 155, 117–126 (1999).
P. Missy, M. C. Lanhers, L. Cunat, et al., Effects of subchronic exposure to manganese chloride on tissue distribution of three essentiel elements in rats, Int. J. Toxicol. 19, 313–321 (2000).
P. Missy, M. C. Lanhers, Y. Grignon, et al., In vitro and in vivo studies on chelation of manganese, Hum. Exp. Toxicol. 19, 448–456 (2000).
J. M. Haguenoer and D. Furon, Manganèse, in Toxicologie et Hygiène Industrielle, J. M. Haguenoer and D. Furon, eds., Technique & Documentation, Paris, Vol. 2, pp. 423–473 (1982).
W. N. Solomon, F. Viteri, T. R. Schuler, et al., Bioavailability of nickel in man: effects of foods and chemically-defined dietary constituents on the absorption of inorganic nickel, J. Nutr. 112, 39–59 (1982).
B. Sandström, L. Davidsson, A. Cederblad, et al., Manganese absorption and metabolism in man, Acta Pharmacol. Toxicol. 59, 60–62 (1986).
J. H. Freeland-Graves, F. Behmardi, C. W. Bales, et al., Metabolic balance of manganese in young men consuming diets containing five levels of dietary manganese, J. Nutr. 118, 764–773 (1988).
P. E. Johnson, G. I. Lykken, and E. D. Korynta, Absorption and biological half-life in humans of intrinsic and extrinsic 54Mn tracers from foods of plant origin, J. Nutr. 121, 711–717 (1991).
C. D. Davis, L. Zech, and J. L. Greger, Manganese metabolism in rats: an improved methodology for assessing gut endogenous losses, Proc. Soc. Exp. Biol. Med. 202, 103–108 (1993).
C. G. Elinder, L. Friberg, T. Kjellstrom, et al., Biological Monitoring of Metals, WHO, Geneva (1994).
J. W. Finley, J. S. Caton, Z. Zhou, et al., A surgical model for determination of true absorption and biliary excretion of manganese in conscious swine fed commercial diets, J. Nutr. 127(12), 2334–2341 (1997).
A. B. R. Thomson and L. S. Valberg, Intestinal uptake of iron, cobalt and manganese in the iron-deficient rat, Am. J. Physiol. 223(6), 1327–1329 (1972).
N. Gruden, Interrelationship of manganese and iron in rat’s duodenum, Nutr. Rep. Int. 15(5), 577–580 (1977).
N. Gruden, Suppression of transduodenal manganese transport by milk diet supplemented with iron, Nutr. Metab. 21, 305–309 (1977).
S. G. Schafer and W. Forth, The influence of tin, nickel, and cadmium on the intestinal absorption of iron, Ecotox. Environ. Safety 7, 87–95 (1983).
S. Spears, Nickel as a newer trace element in the nutrition of domestic animals, J. Anim. Sci. 59(3), 823–835 (1984).
F. H. Nielsen, T. R. Shuler, T. G. McLeod, et al., Nickel influences iron metabolism through physiologic, pharmacologic and toxicologic mechanisms in the rat, J. Nutr. 114, 1280–1288 (1984).
K. M. Halpin, D. G. Chausow, and D. H. Baker, Efficiency of manganese absorption in chicks fed corn-soy and casein diets, J. Nutr. 116(9), 1747–1751 (1986).
H. Kabata, K. I. Inui, and Y. Itokawa, The binding of manganese to the brush-border membrane vesicles of rat small intestine, Nutr. Res. 9, 791–799 (1989).
E. L. B. Novell, N. Y. Rodrigues, G. S. Bianchi, et al., Influence of nickel chloride on iron deficiency in rats, Bol. Estud. Med. Biol. 37, 95–99 (1989).
J. S. Oosting, A. G. Lemmens, G. J. Van den Berg, et al., Iron, copper, and zinc status in rats fed supplemental nickel, Biol. Trace Element Res. 31, 63–70 (1991).
C. D. Davis, T. L. Wolf, and J. L. Greger, Varying levels of manganese and iron affect absorption and gut endogenous losses of manganese by rats, J. Nutr. 122, 1300–1308 (1992).
C. Kies, Bioavailability of manganese, in Manganese in Health and Disease, D. J. Klimis-Tavantzis, ed., CRC, Boca Raton, FL, pp. 39–58 (1994).
J. Tallkvist and H. Tjälve, Enhanced intestinal nickel absorption in iron-deficient rats, Pharmacol. Toxicol. 75(5), 244–249 (1994).
J. Tallkvist and H. Tjälve, Effect of dietary iron-deficiency on the disposition of nickel in rats, Toxicol. Lett. 92(2), 131–138 (1997).
M. W. Smith, K. B. Shenoy, E. S. Debnam, et al., Divalent metal inhibition of non-haem iron uptake across the rat duodenal brush border membrane, Br. J. Nutr. 88(1), 51–56 (2002).
R. A. Gibbons, S. N. Dixon, K. Hallis, et al., Manganese metabolism in cows and goats, Biochim. Biophys. Acta 444, 1–10 (1976).
M. E. Andersen, J. M. Gearhart, and H. J. Clewell, Pharmacokinetic data needs to support risk assessments for inhaled and ingested manganese, Neurotoxicology 20(2–3), 161–172 (1999).
S. Ferruzza, M. Scacchi, M. L. Scarino, et al., Iron and copper alter tight junction permeability in human intestinal Caco-2 cells by distinct mechanisms, Toxicol. In Vitro 16(4), 399–404 (2002).
E. C. Foulkes and D. M. McMullen, On the mechanism of nickel absorption in the rat jejunum, Toxicology 38, 35–42 (1986).
J. Tallkvist and H. Tjälve, Nickel absorption from perfused rat jejunal and ileal segments, Pharmacol. Toxicol. 75(5), 233–243 (1994).
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Arnich, N., Cunat, L., Lanhers, MC. et al. Comparative in situ study of the intestinal absorption of aluminum, manganese, nickel, and lead in rats. Biol Trace Elem Res 99, 157–171 (2004). https://doi.org/10.1385/BTER:99:1-3:157
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DOI: https://doi.org/10.1385/BTER:99:1-3:157