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Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).

J B Moberly, J Logan, P R Borum, K O Story, L E Webb, S V Jassal, L Mupas, H Rodela, G A Alghamdi, J E Moran, M Wolfson, L Martis and D G Oreopoulos
JASN June 1998, 9 (6) 1093-1099; DOI: https://doi.org/10.1681/ASN.V961093
J B Moberly
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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J Logan
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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P R Borum
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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K O Story
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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L E Webb
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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S V Jassal
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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L Mupas
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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H Rodela
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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G A Alghamdi
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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J E Moran
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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M Wolfson
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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L Martis
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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D G Oreopoulos
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085-6730, USA.
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Abstract

Glutathione is a major cellular antioxidant that protects protein thiols and inhibits cellular damage due to oxygen free radicals. It has been reported previously that patients undergoing dialysis have low levels of blood glutathione, which may lead to increased susceptibility to oxidant stress. L-2-oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises cellular glutathione levels by increasing delivery of cysteine, the rate-limiting substrate for glutathione synthesis. This study investigates the effect of OTZ on blood glutathione in a blinded, placebo-controlled study of patients with chronic renal failure treated by peritoneal dialysis. Twenty patients were randomly selected to receive OTZ (0.5 g three times a day orally with meals) or placebo for 14 d. Patients visited the clinic for predose blood collection and safety evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose [follow-up]). Glutathione concentrations were determined in whole blood by HPLC. OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/- 129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139 mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo group at any patient visit, and levels in the OTZ-treated group returned to baseline at follow-up. There were no serious adverse events attributable to OTZ, and the drug appeared to be well tolerated by patients with renal failure treated by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases blood glutathione levels, which may improve antioxidant status in dialysis patients.

  • Copyright © 1998 by American Society of Nephrology
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Journal of the American Society of Nephrology
Vol. 9, Issue 6
1 Jun 1998
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Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).
J B Moberly, J Logan, P R Borum, K O Story, L E Webb, S V Jassal, L Mupas, H Rodela, G A Alghamdi, J E Moran, M Wolfson, L Martis, D G Oreopoulos
JASN Jun 1998, 9 (6) 1093-1099; DOI: 10.1681/ASN.V961093

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Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).
J B Moberly, J Logan, P R Borum, K O Story, L E Webb, S V Jassal, L Mupas, H Rodela, G A Alghamdi, J E Moran, M Wolfson, L Martis, D G Oreopoulos
JASN Jun 1998, 9 (6) 1093-1099; DOI: 10.1681/ASN.V961093
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Cited By...

  • Effect of Procysteine on aging-associated changes in hepatic GSH and SMase: evidence for transcriptional regulation of smpd3
  • Transport via SLC5A8 (SMCT1) Is Obligatory for 2-Oxothiazolidine-4-Carboxylate to Enhance Glutathione Production in Retinal Pigment Epithelial Cells
  • Increased Oxidative Damage to Peripheral Blood Leukocyte DNA in Chronic Peritoneal Dialysis Patients
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