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

Z. Gregus, F. Varga

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43 Citations (Scopus)

Abstract

The effect of hepatic glutathione (GSH) depletion and enzyme induction on hepatic glutathione S-transferase (GST) activity, biliary excretion of GSH, methyl mercury, cadmium and zinc 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-16α-carbonitrile (PCN) and trans-stilbene oxide (TSO) increased 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 mercury, cadmium and zinc 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 mercury and zinc into bile, but decreased that of cadmium. These results do not provide evidence for the role of hepatic GST but strongly support the importance of biliary GSH excretion in the hepatobiliary transport of methyl mercury, cadmium and zinc. It is assumed that phenobarbital and PCN enhance the biliary excretion of these metals by increasing the transport of GSH, the carrier molecule, from liver to bile.

Original languageEnglish
Pages (from-to)398-403
Number of pages6
JournalActa Pharmacologica et Toxicologica
Volume56
Issue number5
Publication statusPublished - 1985

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Pregnenolone Carbonitrile
Phenobarbital
Glutathione Transferase
Mercury
Cadmium
Glutathione
Zinc
Benzo(a)pyrene
diethyl maleate
Bile
Liver
Enzymes
Enzyme Induction
Rats
Metals
Molecules
Hepatobiliary Elimination
16-pregnolone
Substrates
stilbene oxide

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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title = "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 mercury, cadmium and zinc 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-16α-carbonitrile (PCN) and trans-stilbene oxide (TSO) increased 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 mercury, cadmium and zinc 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 mercury and zinc into bile, but decreased that of cadmium. These results do not provide evidence for the role of hepatic GST but strongly support the importance of biliary GSH excretion in the hepatobiliary transport of methyl mercury, cadmium and zinc. It is assumed that phenobarbital and PCN enhance the biliary excretion of these metals by increasing the transport of GSH, the carrier molecule, from liver to bile.",
author = "Z. Gregus and F. Varga",
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T1 - Role of glutathione and hepatic glutathione S-transferase in the biliary excretion of methyl mercury, cadmium and zinc

T2 - A study with enzyme inducers and glutathione depletors

AU - Gregus, Z.

AU - Varga, F.

PY - 1985

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N2 - The effect of hepatic glutathione (GSH) depletion and enzyme induction on hepatic glutathione S-transferase (GST) activity, biliary excretion of GSH, methyl mercury, cadmium and zinc 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-16α-carbonitrile (PCN) and trans-stilbene oxide (TSO) increased 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 mercury, cadmium and zinc 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 mercury and zinc into bile, but decreased that of cadmium. These results do not provide evidence for the role of hepatic GST but strongly support the importance of biliary GSH excretion in the hepatobiliary transport of methyl mercury, cadmium and zinc. It is assumed that phenobarbital and PCN enhance the biliary excretion of these metals by increasing the transport of GSH, the carrier molecule, from liver to bile.

AB - The effect of hepatic glutathione (GSH) depletion and enzyme induction on hepatic glutathione S-transferase (GST) activity, biliary excretion of GSH, methyl mercury, cadmium and zinc 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-16α-carbonitrile (PCN) and trans-stilbene oxide (TSO) increased 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 mercury, cadmium and zinc 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 mercury and zinc into bile, but decreased that of cadmium. These results do not provide evidence for the role of hepatic GST but strongly support the importance of biliary GSH excretion in the hepatobiliary transport of methyl mercury, cadmium and zinc. It is assumed that phenobarbital and PCN enhance the biliary excretion of these metals by increasing the transport of GSH, the carrier molecule, from liver to bile.

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