Role of Glutathione in the Detoxication by Metallothionein of Hepatic Copper.
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Accession number;00A0193260
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| Title;Role of Glutathione in the Detoxication by Metallothionein of Hepatic Copper. |
| Author;
KATO NAOYUKI
(Toho Univ., Sch. of Med.)
NAKAI SHUZO
(Toho Univ., Sch. of Med.)
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Journal Title;Pharmacometrics
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Journal Code:S0617A
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ISSN:0300-8533
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VOL.58;NO.1;PAGE.23-30(1999)
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| Figure&Table&Reference;FIG.6, TBL.1, REF.37 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;One of biological functions of metallothionein(MT) is to protect cells from the toxic effects of the abnormally accumulated metals such as copper, mercury and lead. Glutathione(GSH) is supposed to play some role in the induction of MT. We studied the role of GSH in the copper-detoxication process by MT in rats, using male Wistar rats(332-383g) of 13 weeks old. Copper(II) sulfate(3.0mg/kg as Cu), diethyl maleate(DEM, 689mg/kg) and cycloheximide(CHX, 1.56mg/kg) were administered separately and intraperitoneally to each rat. DEM and CHX were used as a GSH depletor and an inhibitor of protein synthesis, respectively. Copper(II) sulfate and DEM as well as copper(II) sulfate and CHX were simultaneously administered to each rat. The hepatic concentrations of copper, GSH and MT at 6hr after the injection were determined in each case by inductively coupled plasma-mass spectrometry(ICP-MS), glyoxalase method and silver-saturation method, respectively. Copper administration increased the hepatic copper concentration(from 4.40 to 42.8.MU.g/g). Both DEM and CHX neither had appreciable effect on the hepatic copper concentration in the copper-untreated control rats, nor affected the hepatic copper increase. Both copper and DEM decreased hepatic GSH concentration and their simultaneous coadministration further decreased the GSH concentrations by 3.4% of the control rats and by 7.9% of copper-treated rats. The simultaneous coadministration of copper and CHX increased the GSH concentration by 1.5 times of copper-treated rats. DEM elevated hepatic MT concentration and CHX had no effect on the MT concentration. Copper administration increased hepatic MT concentration by 15 times. DEM and CHX reduced the increased MT concentrations by 8.5 and 10% of copper-treated rats, respectively.... (author abst.) |
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