title: Effect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorption.
abstract: BACKGROUND
  Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of delta-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues.
  
  
  METHODS
  We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed.
  
  
  RESULTS
  While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 micromoles kg(-1) body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression.
  
  
  CONCLUSIONS
  The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important.
authors.affiliation: King's College, London, UK. yemisi.latunde-dada@kcl.ac.uk
authors.forename: G O
authors.initials: GO
authors.lastname: Latunde-Dada
authors.forename: S
authors.initials: S
authors.lastname: Shirali
authors.forename: A T
authors.initials: AT
authors.lastname: McKie
authors.forename: R J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: T J
authors.initials: TJ
authors.lastname: Peters
mesh_terms: D000818:Animals; D003035:Cobalt / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D007408:Intestinal Absorption / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009532:Nickel / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D003035:Cobalt; D012313:RNA; C022838:nickel chloride; D009532:Nickel; D007501:Iron