Pyridoxal isonicotinoyl hydrazone (Synonyms: NSC 77674, PIH)

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

Pyridoxal isonicotinoyl hydrazone (PIH) is a tridentate Fe-chelating agent that shows high Fe chelation efficacy. In 59Fe-labeled reticulocytes, PIH (0.1 mmol/L) released 38.6% of cellular 59Fe [1]. PIH inhibited the formation of ascorbyl radical and Fe(III)–EDTA-mediated ascorbate oxidation in a dose-dependent way [3].

In Fe-loaded rats, PIH orally administrated resulted in an eightfold increase in fecal Fe excretion and possibly some urinary excretion of Fe [1]. In mice loaded with iron-acetohydroxamic acid complex, pyridoxal isonicotinoyl hydrazone (po.) were given daily for four days at 300 mg/kg/day. Total iron excreted over the 4-day period (micrograms/mouse) was 31 [2]. Pyridoxal isonicotinoyl hydrazine could be used for experimental chelating therapy in iron-overload diseases [3].

References:
[1].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.
[2].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.
[3].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.