Biliary Iron Excretion in Rats following Pyridoxal Isonicotinoyl Hydrazone

Abstract

Summary 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.