NDLI: Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury.

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Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury.

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Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Horwitz, Lawrence D. Nelson, Sally K. Horwitz, Marcus A. Kupiec-weglinski, Jerzy W. Busuttil, Ronald W. Amersi, Farin Melinek, Judy Shen, Xiu Da Kato, Hirohisa
Description	Author Affiliation: Amersi F ( The Dumont-University of California, Los Angeles Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, Los Angeles, CA 90095, USA.);
Abstract	Ischemia/reperfusion (I/R) injury is a serious potential threat to outcomes in organ transplantation and other clinical arenas in which there is temporary interruption of blood flow. I/R is a frequent cause of primary failure in organ transplantation. We hypothesized that the antioxidant bucillamine, a potent sulfhydryl donor, would protect against I/R injury in high-risk organ transplants. Because livers subjected to prolonged ischemia and very fatty livers are highly susceptible to severe I/R injury, we studied the effect of bucillamine in three animal models of liver transplantation: two ex vivo models of isolated perfused livers, either normal or fatty rat livers, and an in vivo model of syngenic orthotopic liver transplants in rats. In all models, livers were deprived of oxygen for 24 h before either ex vivo reperfusion or transplantation. In the ex vivo models, bucillamine treatment significantly improved portal vein blood flow and bile production, preserved normal liver architecture, and significantly reduced liver enzyme release and indices of oxidative stress. Moreover, bucillamine treatment significantly increased levels of reduced glutathione in the liver and lowered levels of oxidized glutathione in both liver and blood. In rats subjected to liver transplants, bucillamine significantly enhanced survival and protected against hepatic injury. Possible mechanisms of this protection include prevention of excessive accumulation of toxic oxygen species, interruption of redox signaling in hepatocytes, and inhibition of macrophage activation. This study demonstrates the potential utility of bucillamine or other cysteine-derived thiol donors for improving outcomes in organ transplantation and other clinical settings involving I/R injury.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antioxidants Therapeutic Use Cysteine Organ Transplantation Adverse Effects Reperfusion Injury Prevention & Control Animals Analogs & Derivatives Disease Models, Animal Glutathione Metabolism Rats, Sprague-Dawley Rats, Zucker Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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