Journal article
Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury
Proceedings of the National Academy of Sciences - PNAS, Vol.99(13), pp.8915-8920
06/25/2002
DOI: 10.1073/pnas.132026099
PMCID: PMC124398
PMID: 12084933
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.
Details
- Title: Subtitle
- Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury
- Creators
- Farin Amersi - University of California, Los AngelesSally K. Nelson - University of California, Los AngelesXiu Da Shen - University of California, Los AngelesHirohisa Kato - University of California, Los AngelesJudy Melinek - University of California, Los AngelesJerzy W. Kupiec-WeglinskiLawrence D. Horwitz - University of California, Los AngelesRonald W. Busuttil - University of California, Los AngelesMarcus A. Horwitz - University of California, Los Angeles
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.99(13), pp.8915-8920
- Publisher
- National Academy of Sciences
- DOI
- 10.1073/pnas.132026099
- PMID
- 12084933
- PMCID
- PMC124398
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Language
- English
- Date published
- 06/25/2002
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984656597502771
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