Current Antioxidant Treatments in Organ Transplantation

Shi, Shaojun; Xue, Feng

doi:10.1155/2016/8678510

Cited by 41 publications

(36 citation statements)

References 60 publications

(60 reference statements)

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“…Another situation of oxidative-stress-related cardiac damage is heart transplantations, where the donor heart, graft, is exposed to cold ischemia-reperfusion injury associated with increased ROS. This leads to graft dysfunction, like allograft rejection, delayed graft function, or primary nonfunction, as well as to endothelial and parenchymal cell injury [52,53]. To increase success of the heart transplantation, experimental studies have focused on the enrichment of antioxidative substrates in cardioplegia solution and pump prime solution [54][55][56][57][58][59], suggesting the importance of continuous research into antioxidants.…”

Section: Int J Mol Sci 2020 21 X For Peer Review 3 Of 19mentioning

confidence: 99%

Oxidative Stress-Responsive MicroRNAs in Heart Injury

Kura

Bačová

Kaločayová

et al. 2020

IJMS

125

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Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many signaling pathways. However, if overproduced, they also play a significant role in the development of cardiovascular diseases, such as arrhythmia, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction and heart transplantation), and heart failure. As a result of oxidative stress action, apoptosis, hypertrophy, and fibrosis may occur. MicroRNAs (miRNAs) represent important endogenous nucleotides that regulate many biological processes, including those involved in heart damage caused by oxidative stress. Oxidative stress can alter the expression level of many miRNAs. These changes in miRNA expression occur mainly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, calcineurin/nuclear factor of activated T cell (NFAT), or nuclear factor kappa B (NF-κB) pathways. Up until now, several circulating miRNAs have been reported to be potential biomarkers of ROS-related cardiac diseases, including myocardial infarction, hypertrophy, ischemia/reperfusion, and heart failure, such as miRNA-499, miRNA-199, miRNA-21, miRNA-144, miRNA-208a, miRNA-34a, etc. On the other hand, a lot of studies are aimed at using miRNAs for therapeutic purposes. This review points to the need for studying the role of redox-sensitive miRNAs, to identify more effective biomarkers and develop better therapeutic targets for oxidative-stress-related heart diseases.

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Section: Int J Mol Sci 2020 21 X For Peer Review 3 Of 19mentioning

confidence: 99%

Oxidative Stress-Responsive MicroRNAs in Heart Injury

Kura

Bačová

Kaločayová

et al. 2020

IJMS

125

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“…Our finding that NAC causes autophagy inhibition and leads to LEC necrosis during IRI has important clinical implications. It suggests that general antioxidants targeted to the liver may not be an effective intervention to reduce IRI because although it may aid hepatocyte survival, it will induce LEC death and potentially exacerbate the proinflammatory liver microenvironment …”

Section: Discussionmentioning

confidence: 99%

The Reactive Oxygen Species–Mitophagy Signaling Pathway Regulates Liver Endothelial Cell Survival During Ischemia/Reperfusion Injury

Bhogal

Weston²,

Velduis

et al. 2018

Liver Transpl

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Ischemia/reperfusion injury (IRI) is the main cause of complications following liver transplantation. Reactive oxygen species (ROS) were thought to be the main regulators of IRI. However, recent studies demonstrate that ROS activate the cytoprotective mechanism of autophagy promoting cell survival. Liver IRI initially damages the liver endothelial cells (LEC), but whether ROS-autophagy promotes cell survival in LEC during IRI is not known. Primary human LEC were isolated from human liver tissue and exposed to an in vitro model of IRI to assess the role of autophagy in LEC. The role of autophagy during liver IRI in vivo was assessed using a murine model of partial liver IRI. During IRI, ROS specifically activate autophagy-related protein (ATG) 7 promoting autophagic flux and the formation of LC3B-positive puncta around mitochondria in primary human LEC. Inhibition of ROS reduces autophagic flux in LEC during IRI inducing necrosis. In addition, small interfering RNA knockdown of ATG7 sensitized LEC to necrosis during IRI. In vivo murine livers in uninjured liver lobes demonstrate autophagy within LEC that is reduced following IRI with concomitant reduction in autophagic flux and increased cell death. In conclusion, these findings demonstrate that during liver IRI ROS-dependent autophagy promotes the survival of LEC, and therapeutic targeting of this signaling pathway may reduce liver IRI following transplantation.

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“…Hepatic IRI is one of the most common causes for organ dysfunction and failure after orthotopic liver transplantation (OLT) and may compromise the outcome after extended liver resections and OLT [ 15 , 16 , 49 ]. Therefore, strategies to minimize the negative effects of ischemia are now in the forefront of clinical and experimental studies.…”

Section: Discussionmentioning

confidence: 99%

“…This ROS-mediated liver damage not only leads to limited postoperative liver function but is also regarded as an immediate origin of allograft rejection, delayed graft function, and primary nonfunction after liver transplantation [ 2 , 15 ]. Therefore, several antioxidant treatments are currently under investigation to improve the outcome after liver transplantation [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Glutathione Hemostasis by Inhibition of 12/15‐Lipoxygenase Prevents ROS‐Mediated Cell Death after Hepatic Ischemia and Reperfusion

Drefs

Thomas

Guba

et al. 2017

Oxidative Medicine and Cellular Longevity

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Background Reactive oxygen species- (ROS-) mediated ischemia-reperfusion injury (IRI) detrimentally impacts liver transplantation and resection. 12/15-Lipoxygenase (12/15-LOX), an antagonistic protein of the glutathione peroxidase 4 (GPX4) signaling cascade, was proven to mediate cell death in postischemic cerebral and myocardial tissue. The aim of this study was to investigate the impact of 12/15-LOX inhibition on hepatic IRI. Methods Livers of C57BL/6 mice were exposed to 60 minutes of partial warm ischemia and 90 minutes of reperfusion after previous Baicalein administration, an inhibitor of 12/15-LOX. Tissue samples were analyzed by TUNEL assay, Western blot, and spectral photometry. Results TUNEL labeling showed a significant reduction of hepatic cell death following baicalein pretreatment. Western Blot analysis revealed a significant downregulation of Jun-amino-terminal-kinase (JNK), caspase-3, and poly-ADP-ribose-polymerase (PARP), besides considerably lowered p44/42-MAP-kinase (ERK1/2) expression after Baicalein administration. A significant elevation of glutathione oxidation was measured in Baicalein pretreated livers. Conclusion Our data show that inhibition of 12/15-lipoxygenase causes significant cell death reduction after hepatic ischemia and reperfusion by enhancing glutathione metabolism. We conclude that GPX4-dependent cell death signaling cascade might play a major role in development of hepatic IRI, in which the investigated proteins JNK, caspase-3, ERK1/2, and PARP might contribute to tissue damage.

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Current Antioxidant Treatments in Organ Transplantation

Cited by 41 publications

References 60 publications

Oxidative Stress-Responsive MicroRNAs in Heart Injury

Oxidative Stress-Responsive MicroRNAs in Heart Injury

The Reactive Oxygen Species–Mitophagy Signaling Pathway Regulates Liver Endothelial Cell Survival During Ischemia/Reperfusion Injury

Modulation of Glutathione Hemostasis by Inhibition of 12/15‐Lipoxygenase Prevents ROS‐Mediated Cell Death after Hepatic Ischemia and Reperfusion

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