Biliary iron excretion in rats following pyridoxal isonicotinoyl hydrazone

Biliary excretion of iron after administration of pyridoxal isonicotinoyl hydrazone (PIH), a recently identified effective iron-chelating agent, was investigated in rats. PIH administered both intraperitoneally and orally was shown to increase significantly 59Fe excretion into bile of rats which had previously been injected with 59Fe-transferrin to label hepatic parenchymal cells. 59Fe-PIH appears in bile as early as 15 min after chelator administration and the peak of 59Fe-radioactivity in bile is seen 1--5 h following intraperitoneal PIH injection. PIH, administered intraperitoneally, 125--250 mg/kg, increased 24 h biliary radioiron excretion about 35 times and in addition increased urinary and faecal iron excretion. When PIH was given immediately before 59Fe-transferrin, 24 h cumulative biliary 59Fe excretion was even higher. PIH was also demonstrated to increase biliary excretion of radioiron released from 59Fe-haemoglobin catabolysed in reticuloendothelial cells. The effect of PIH was confirmed by estimation of biliary iron concentration using the method of atomic absorption spectrophotometry. Repeated PIH administration to rats decreased 59Fe radioactivity in liver and kidney and increased urinary and faecal iron excretion.