Effect of glutathione depletion on metallothionein synthesis induced by paraquat in mice

The Tohoku Journal of Experimental Medicine
I NakagawaA Naganuma

Abstract

The effect of Glutathione (GSH) depletion on the induction of metallothionein (MT) synthesis by paraquat (PQ) was examined in ICR mice. An increase in hepatic MT level in mice was observed after a single PQ administration. Pretreatment of mice with L-buthionine-SR-sulfoximine (BSO), an inhibitor of GSH synthesis, enhanced the induction of hepatic and renal MT synthesis by PQ depending on the decreased tissue GSH level. A similar result was obtained by pretreatment with diethylmaleate, a GSH depleting agent. The ratio of hepatic MT-I to MT-II induced by PQ was not changed by BSO pretreatment. An increase in the hepatic MT level in GSH depleted mice was observed from 3 hr to 24 hr after PQ administration. An increase in the hepatic MT-I mRNA level after treatment with PQ was observed prior to hepatic MT induction in BSO pretreated mice. Pretreatment with actinomycin D, an inhibitor of mRNA synthesis, inhibits the PQ-induced increase in hepatic MT and MT-I mRNA levels in BSO pretreated mice. Pretreatment with BSO did not affect the induction of MT synthesis by zinc, cadmium or dexamethasone. Pretreatment with dexamethasone, an anti-inflammatory agent, enhanced the hepatic MT induction by PQ treatment in GSH depleted mice, while de...Continue Reading

Citations

May 12, 2000·Toxicology in Vitro : an International Journal Published in Association with BIBRA·A E BayoumiD Ordóñez
Oct 12, 2010·Ageing Research Reviews·William R Swindell
Jun 7, 2008·Experimental Biology and Medicine·Ercan GöcgeldiMetin Hasde
May 20, 1998·Biochemical and Biophysical Research Communications·Y OkazakiA Naganuma

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