Pyridoxal isonicotinoyl hydrazone

Pyridoxal isonicotinoyl hydrazine is a cell-permeable and relatively non-toxic iron (Fe3+) chelator [1].

Pyridoxal isonicotinoyl hydrazone (PIH) is a tridentate iron chelator with high Fe-chelating efficacy. In 59Fe-labeled reticulocytes, PIH (0.1 mmol/L) released 38.6% of intracellular 59Fe [1]. PIH inhibits ascorbyl radical formation and Fe(III)–EDTA-mediated ascorbate oxidation in a dose-dependent manner [3].

In iron-loaded rats, oral administration of PIH resulted in an 8-fold increase in fecal iron excretion, and possibly some iron excretion in urine as well [1]. In mice loaded with an iron–acetohydroxamic acid complex, oral administration of pyridoxal isonicotinoyl hydrazone for 4 days at 300 mg/kg per day led to a total iron excretion of 31 μg/mouse over 4 days [2]. Pyridoxal isonicotinoyl hydrazine can be used for experimental chelation therapy in iron overload disease [3].

References:
Richardson DR, Ponka P.? Pyridoxal isonicotinoyl hydrazone and its analogs: potential orally effective iron-chelating agents for the treatment of iron overload disease. J Lab Clin Med. 1998 Apr;131(4):306-15.
Gale GR, Litchenberg WH, Smith AB, et al.? Comparative iron mobilizing actions of deferoxamine, 1,2-dimethyl-3-hydroxypyrid-4-one, and pyridoxal isonicotinoyl hydrazone in iron hydroxamate-loaded mice. Res Commun Chem Pathol Pharmacol. 1991 Sep;73(3):299-313.
Maurício AQ, Lopes GK, Gomes CS, et al.? Pyridoxal isonicotinoyl hydrazone inhibits iron-induced ascorbate oxidation and ascorbyl radical formation. Biochim Biophys Acta. 2003 Mar 17;1620(1-3):15-24.