pyridoxal isonicotinoyl hydrazone (PIH) is a cell-permeable and relatively non-toxic iron (Fe3+) chelator that shows high iron chelation efficacy both in vitro and in vivo.

After a 60-minute reincubation of 59Fe-labeled reticulocytes with tris-hydroxamate deferoxamine (5 mmol/L), 3.5% of cellular 59Fe was released, although Pyridoxal isonicotinoyl hydrazone (PIH) at a 50-fold lower concentration (0.1 mmol/L) released 38.6% of cellular 59Fe [1]. In primary human hepatocytes and the human hepatocellular carcinoma cell line HepG2/C3A, PIH treatment decreases Fech protein levels, but not Fech mRNA levels; and PIH is detected after isoniazid treatment, with levels increasing further when exogenous vitamin B6 analogs are coadministered [2].

Intraperitoneal administration of PIH to mice (5 mg/25 gm mouse/day) over 6 days decreased 59Fe levels in the liver, spleen, and kidney but not in the blood. After oral administration, PIH resulted in an eightfold increase in fecal Fe excretion and possibly some urinary excretion of Fe [1].