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Abstract

Disposition of glutathione monoethyl ester in the rat: glutathione ester is a slow release form of extracellular glutathione.

I Grattagliano, P Wieland, C Schranz and B H Lauterburg
Journal of Pharmacology and Experimental Therapeutics February 1995, 272 (2) 484-488;
I Grattagliano
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P Wieland
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C Schranz
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B H Lauterburg
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Abstract

Glutathione monethyl ester (GSHE) is though to deliver glutathione (GSH) directly and intact into cell cytosol and therefore might have therapeutic potential in states of GSH deficiency. To better understand the disposition of GSHE, the pharmacokinetics of GSHE and GSH were compared in rats. Fifteen min after an i.v. dose of 5 mmol/kg GSHE, the plasma concentration of GSHE was 7.2 +/- 1.2 mmol/l and the plasma concentration of GSH had increased from 0.009 +/- 0.002 to 2.5 +/- 0.3 mmol/l. The areas under the plasma concentration time curves of GSH were identical after either the administration of GSHE or GSH, but the mean residence time of GSH in plasma was significantly longer after GSHE. The concentration of GSHE in liver reached a peak of 0.66 +/- 0.09 mumol/g. Intrahepatic concentrations of cysteine and GSH increased from 53 +/- 15 to 319 +/- 41 nmol/g and from 5.5 +/- 0.4 to 7.8 +/- 1.5 mumol/g, respectively, and remained elevated for 2 hr. Similar increases occurred after administration of GSH. However, the concentrations of cysteine and GSH peaked earlier and had returned to baseline by 2 hr. Qualitatively similar results were obtained in rats pretreated with L-buthionine-[S, R]-sulfoximine that partially inhibits GSH synthesis. GSHE added to rat plasma at a concentration of 10 mM was hydrolyzed to GSH at a rate of 0.1 mumol/min. Our data indicate that GSHE is not readily taken up by the liver, but is hydrolyzed by esterases in plasma and thereby gradually releases GSH in the extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 272, Issue 2
1 Feb 1995
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Abstract

Disposition of glutathione monoethyl ester in the rat: glutathione ester is a slow release form of extracellular glutathione.

I Grattagliano, P Wieland, C Schranz and B H Lauterburg
Journal of Pharmacology and Experimental Therapeutics February 1, 1995, 272 (2) 484-488;

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Abstract

Disposition of glutathione monoethyl ester in the rat: glutathione ester is a slow release form of extracellular glutathione.

I Grattagliano, P Wieland, C Schranz and B H Lauterburg
Journal of Pharmacology and Experimental Therapeutics February 1, 1995, 272 (2) 484-488;
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