A Novel Iron Chelator in Combination With a P-Selectin Antagonist Prevents Ischemia/Reperfusion Injury in a Rat Liver Model1

Amersi, Farin; Dulkanchainun, T S; Nelson, Sally K.; Farmer, Douglas G.; Kato, Hirohisa; Zaky, Joseph; Melinek, Judy; Shaw, Gray D.; Kupiec‐Weglinski, Jerzy W.; Horwitz, Lawrence D.; Horwitz, Marcus A.; Busuttil, Ronald W.

doi:10.1097/00007890-200101150-00018

Cited by 33 publications

(2 citation statements)

References 25 publications

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“…In contrast, bucillamine probably prevents injury caused by ROS generation from both leukocyte and nonleukocyte sources. Indeed, bucillamine alone in this study was at least as effective as the combination of a P-selectin antibody and a potent iron chelator that reduced oxidant injury in a previous study that used the same ex vivo model of I͞R injury in normal rat livers (48). In conclusion, bucillamine significantly reduces hepatic I͞R injury in ex vivo models involving both normal and steatotic rat livers and markedly improves outcomes after syngenic OLTs.…”

Section: Discussionsupporting

confidence: 52%

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

Amersi

Nelson

Shen

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Ischemia͞reperfusion (I͞R) injury is a serious potential threat to outcomes in organ transplantation and other clinical arenas inwhich there is temporary interruption of blood flow. I͞R is a frequent cause of primary failure in organ transplantation. We hypothesized that the antioxidant bucillamine, a potent sulfhydryl donor, would protect against I͞R injury in high-risk organ transplants. Because livers subjected to prolonged ischemia and very fatty livers are highly susceptible to severe I͞R 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 I͞R injury.

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Section: Discussionsupporting

confidence: 52%

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

Amersi

Nelson

Shen

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…In one study, recombinant P-selection glycoprotein ligand immunoglobulin (rPSGL-Ig), as a glycoprotein that binds P-selectin, was found to inhibit neutrophil adhesion. Moreover, desferriexochelin 772SM (D-Exo) enhanced the capacity of rPSGL-Ig to better protect against liver IRI [ 99 ]. Degranulation of activated neutrophils may release numerous proteases, including cathepsin G, elastase, heparinase, and hydrolytic enzymes [ 100 ].…”

Section: Hepatic Microenvironmentmentioning

confidence: 99%

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Gao¹,

Qiu²,

Wang³

et al. 2022

Aging and disease

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Hepatic ischemia/reperfusion injury (IRI) is mainly characterized by high activation of immune inflammatory responses and metabolic responses. Understanding the molecular and metabolic mechanisms underlying development of hepatic IRI is critical for developing effective therapies for hepatic IRI. Recent advances in research have improved our understanding of the pathogenesis of IRI. During IRI, hepatocyte injury and inflammatory responses are mediated by crosstalk between the immune cells and metabolic components. This crosstalk can be targeted to treat or reverse hepatic IRI. Thus, a deep understanding of hepatic microenvironment, especially the immune and metabolic responses, can reveal new therapeutic opportunities for hepatic IRI. In this review, we describe important cells in the liver microenvironment (especially non-parenchymal cells) that regulate immune inflammatory responses. The role of metabolic components in the diagnosis and prevention of hepatic IRI are discussed. Furthermore, recent updated therapeutic strategies based on the hepatic microenvironment, including immune cells and metabolic components, are highlighted.

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Ischemia/Reperfusion Injury

Anaya-Prado¹,

Toledo‐Pereyra²,

Lentsch³

et al. 2002

Journal of Surgical Research

203

163

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A Novel Iron Chelator in Combination With a P-Selectin Antagonist Prevents Ischemia/Reperfusion Injury in a Rat Liver Model1

Cited by 33 publications

References 25 publications

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

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

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Ischemia/Reperfusion Injury

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