title: Different behaviour of 63Ni and 59Fe during absorption in iron-deficient and iron-adequate jejunal rat segments ex vivo.
abstract: Nickel exhibits low oral toxicity. It shares the absorptive pathways for iron, though there are substantial quantitative differences in handling of both metals. To analyse these differences more closely, jejunal segments from iron-deficient and iron-adequate rats were luminally perfused ex vivo with 59Fe and 63Ni at six different concentrations (1-500 micromo1/l) under steady state conditions. 59Fe over-all absorption increased 2.0-4.6-fold in iron-deficiency at luminal concentrations between 1 and 100 micromol/l, while 63Ni absorption increased to a much lower extent (2.6-fold at 1 micromol/l and 1.5-fold at higher luminal concentrations). Moreover, there was a 5-7-fold higher concentration for 63Ni in the jejunal tissue than in the absorbate at luminal concentrations above 50 micromol/l which was not observed at 1 micromol 63Ni/l and not for 59Fe. 63Ni tissue load showed a linear and a saturable fraction. In iron-deficiency the saturable 63Ni fraction increased 4-fold as compared to only 1.5-fold increments for 59Fe. Moreover, a substantially higher share of 63Ni was retained in the jejunal tissue at high as compare to low luminal concentrations after perfusion had been continued without luminal radioactivity. This was not found for 59Fe and suggests a concentration-dependent block of 63Ni export across the enterocytes' basolateral membrane. To explain these results one may speculate that 63Ni may bind more tightly to tissue ligands than 59Fe due to the higher thermodynamic and kinetic stability of nickel complexes. In particular, nickel may bind to a basolateral population of metal carriers and block its own basolateral transfer in a concentration-dependent manner. Tight 63Ni binding to non-specific jejunal ligands is responsible for the unaltered high linear fraction of jejunal 63Ni load in iron-deficient and iron-adequate segments. Binding of 63Ni to food and tissue ligands in the small intestine may, thus, be a likely explanation for the low oral nickel toxicity.
authors.affiliation: Walther-Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians-Universität, Nussbaumstr 26, 80336, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Müller-Fassbender
authors.forename: B
authors.initials: B
authors.lastname: Elsenhans
authors.forename: A T
authors.initials: AT
authors.lastname: McKie
authors.forename: K
authors.initials: K
authors.lastname: Schümann
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism; D000090463:Iron Deficiencies; D007504:Iron Radioisotopes; D019266:Iron, Dietary; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D009532:Nickel / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D007504:Iron Radioisotopes; D019266:Iron, Dietary; D009532:Nickel; D007501:Iron