Elsevier

Biochemical Pharmacology

Volume 34, Issue 17, 1 September 1985, Pages 3011-3017
Biochemical Pharmacology

Iron chelation by pyridoxal isonicotinoyl hydrazone and analogues in hepatocytes in culture

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Abstract

Pyridoxal isonicotinoyl hydrazone (PIH) and several analogues were synthesized and assessed in the rat hepatocyte culture for their potential in iron chelation therapy. Pyridoxal isonicotinoyl hydrazone and pyridoxal benzoyl hydrazone were as effective as desferrioxamine (DFO) in reducing both net uptake of rat transferrin-59Fe and incorporation into ferritin by hepatocytes. Dialysis studies showed that this was due to a cellular action and not to the extracellular chelation of transferrin-bound 59Fe. The analogues of PIH were more effective in mobilization studies than PIH and DFO, releasing more 59Fe from ferritin as well as from the stroma-mitochondrial membranes in hepatocytes prelabelled using transierrin-59Fe. Chelator action was dependent on incubation time, concentration, temperature and lipophilicity. Pyridoxal benzoyl hydrazone, the most effective iron chelator, was also the most lipophilic, suggesting that access to cellular iron compartments as well as iron-binding affinity is important in effective iron chelation.

References (29)

  • P. Ponka et al.

    Biochim. biophys. Acta

    (1979)
  • J.-C. Sibille et al.

    FEBS Lett.

    (1982)
  • E.S. Cole et al.

    Biochim. biophys. Acta

    (1983)
  • D. Heinert et al.

    J. Am. chem. Soc.

    (1959)
  • R. Rama et al.

    FEBS Lett.

    (1981)
  • M.L. Vitolo et al.

    J. inorg. Biochem.

    (1984)
  • D.J. Weatherall
  • A. Jacobs

    Br. J. Haematol.

    (1979)
  • A.E. Martell et al.
  • M.J. Pippard et al.

    Br. J. Haematol.

    (1983)
  • E. Baker et al.

    J. Am. chem. Soc.

    (1984)
  • T. Hoy et al.

    Br. J. Haematol.

    (1979)
  • M. Cikrt et al.

    Br. J. Haematol.

    (1980)
  • C. Hershko et al.

    J. Lab. clin. Med.

    (1981)
  • Cited by (0)

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