Role of Glutathione and Hepatic Glutathione S‐transferase in the Biliary Excretion of Methyl Mercury, Cadmium and Zinc: A Study with Enzyme Inducers and Glutathione Depletors

Abstract

The effect of hepatic glutathione (GSH) depletion and enzyme induction on hepatic glutathione S-transferase (GST) activity, biliary excretion of GSH, methyl Hg, Cd and Zn was studied in rats. The GSH depletors, methyl iodide and diethyl maleate, did not influence hepatic GST activity but, depending on the substrate used, benzo(a)pyrene, phenobarbital, pregnenolone-16.alpha.-carbonitrile (PCN) and trans-stillbene oxide (TSO) increased it by 16-33, 44-89, 53-97 and 208-279%, respectively. GSH depletors decreased (-88%), benzo(a)pyrene and TSO did not affect, phenobarbital and PCN increased (+113 and +149%) the transport of GSH into bile. The biliary excretion of methyl Hg, Cd and Zn was reduced by GSH depletors (-97, -74 and -93%), and enhanced by phenobarbital (+139, +280 and +220%) and PCN (+150, +121 and +160%). Treatment with benzo(a)pyrene and TSO did not affect the excretion of methyl Hg and Zn into bile, but decreased that of Cd. No evidence for the role of hepatic GST is provided, but the importance of biliary GSH excretion in the hepatobiliary transport of methyl Hg, Cd and Zn is strongly supported. Phenobarbital and PCN enhanced the biliary excretion of these metals by increasing the transport of GSH, the carrier molecule, from liver to bile.