scholarly journals The Current Knowledge of the Role of PPAR in Hepatic Ischemia-Reperfusion Injury

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
M. Elias-Miró ◽  
M. B. Jiménez-Castro ◽  
M. Mendes-Braz ◽  
A. Casillas-Ramírez ◽  
C. Peralta
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Potential Therapeutic Target ◽  
Hepatic Ischemia ◽  
Ppar Signaling ◽  
Peroxisome Proliferator Activated Receptors ◽  
Hepatic Ischemia Reperfusion

Strategies to improve the viability of steatotic livers could reduce the risk of dysfunction after surgery and increase the number of organs suitable for transplantation. Peroxisome proliferator-activated receptors (PPARs) are major regulators of lipid metabolism and inflammation. In this paper, we review the PPAR signaling pathways and present some of their lesser-known functions in liver regeneration. Potential therapies based on PPAR regulation will be discussed. The data suggest that further investigations are required to elucidate whether PPAR could be a potential therapeutic target in liver surgery and to determine the most effective therapies that selectively regulate PPAR with minor side effects.

scholarly journals PGC-1α Protects against Hepatic Ischemia Reperfusion Injury by Activating PPARα and PPARγ and Regulating ROS Production

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Chaoqun Wang ◽  
Zihao Li ◽  
Baolei Zhao ◽  
Yaohua Wu ◽  
Yao Fu ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Hepatic Ischemia ◽  
Peroxisome Proliferator Activated Receptors ◽  
Hepatic Ischemia Reperfusion ◽  
Serum Aminotransferases

Peroxisome proliferator-activated receptors (PPARs) α and γ have been shown to be protective in hepatic ischemia/reperfusion (I/R) injury. However, the precise role of PPARγ coactivator-1α (PGC-1α), which can coactivate both of these receptors, in hepatic I/R injury, remains largely unknown. This study was designed to test our hypothesis that PGC-1α is protective during hepatic I/R injury in vitro and in vivo. Our results show that endogenous PGC-1α is basally expressed in normal livers and is moderately increased by I/R. Ectopic PGC-1α protects against hepatic I/R and hepatocyte anoxia/reoxygenation (A/R) injuries, whereas knockdown of endogenous PGC-1α aggravates such injuries, as evidenced by assessment of the levels of serum aminotransferases and inflammatory cytokines, necrosis, apoptosis, cell viability, and histological examination. The EMSA assay shows that the activation of PPARα and PPARγ is increased or decreased by the overexpression or knockdown of PGC-1α, respectively, during hepatic I/R and hepatocyte A/R injuries. In addition, the administration of specific antagonists of either PPARα (MK886) or PPARγ (GW9662) can effectively decrease the protective effect of PGC-1α against hepatic I/R and hepatocyte A/R injuries. We also demonstrate an important regulatory role of PGC-1α in reactive oxygen species (ROS) metabolism during hepatic I/R, which is correlated with the induction of ROS-detoxifying enzymes and is also dependent on the activations of PPARα and PPARγ. These data demonstrate that PGC-1α protects against hepatic I/R injury, mainly by regulating the activation of PPARα and PPARγ. Thus, PGC-1α may be a promising therapeutic target for the protection of the liver against I/R injury.

The role of microRNA in hepatic ischemia/reperfusion injury

MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Chrysanthos D. Christou ◽  
Georgios Tsoulfas
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Clinical Manifestations ◽  
Diagnostic Procedures ◽  
Clinical Tool ◽  
Hepatic Ischemia ◽  
Humoral Factors ◽  
Early Graft ◽  
Hepatic Ischemia Reperfusion

Introduction: Ischemia-reperfusion (I/R) injuries are caused by complex interrelated mechanisms and pathways. Regarding the liver, I/R injuries and their clinical manifestations are crucial for the surgical outcome. Despite its importance, there is no broadly accepted therapy either for the prevention or for the management of I/R injury. I/R injury of the liver can occur either during hepatic surgery (warm) or during the transplantation procedure (cold). MicroRNAs play a pivotal role in the mechanism of I/R injury, as they regulate the expression of the cellular participants and humoral factors associated with I/R injury. Objective: In this review, we highlight the microRNAs that are involved in the I/R injury of the liver, and the molecular pathways that they regulate. In addition, we discuss the potential role of circulating microRNAs as biomarkers and their role as pharmacological targets in the prevention, diagnosis and treatment of I/R injuries. Method: We conducted a comprehensive review of the PubMed bibliographic database regarding microRNAs and I/R injuries of the liver. Results: In diagnostics, microRNA panels could replace invasive diagnostic procedures, relieving patients of the associated complications. In therapeutics, microRNA agomirs, antagomirs and other drugs can be used to shift the balance between proapoptotic and survival pathways, to alleviate the liver damage caused by I/R. In transplantation procedures, microRNA profiling could decrease the incidence of early graft dysfunction, especially regarding marginal grafts. Conclusion: Although microRNAs seem a very promising clinical tool in the management of I/R injuries, further research is required, until microRNAs become a novel tool in the diagnosis and monitoring of an I/R injury of the liver.

The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice

2005 ◽  
Vol 124 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Taiji Watanabe ◽  
Sunao Kubota ◽  
Masaki Nagaya ◽  
Shoichi Ozaki ◽  
Hiroko Nagafuchi ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

scholarly journals Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Di Liu ◽  
Xin Jin ◽  
Chunqi Zhang ◽  
You Shang
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Regulatory Protein ◽  
Liver Homogenate ◽  
Hepatic Ischemia ◽  
Damage Degree ◽  
Tnf Α ◽  
Hepatic Ischemia Reperfusion

Purpose: This article aimed to study the role of sevoflurane pre-conditioning in hepatic ischemia–reperfusion and its potential mechanism. Methods: Rat liver ischemia–reperfusion model was constructed. Serum TNF-α, IL-1β, IL-10, and IL-6 concentrations were detected by ELISA. Malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in liver homogenate were determined. Hematoxylin–Eosin (HE) staining, Tunel, and immunohistochemistry were performed. Ischemia–reperfusion hepatocyte model was established. Cells transfection was conducted. Apoptosis was observed by flow cytometry. Quantitative real-time PCR (qRT-PCR) and Western blotting analysis were used. Results: Compared with I/R group, liver damage degree, liver cell apoptosis, and glucose regulatory protein 78 (Grp78) expression was obviously reduced in rats of SEV group. TNF-α, IL-1β, and IL-6 concentrations were also significantly increased (P<0.01). MDA and NO concentrations were dramatically lower (P<0.01) and SOD concentration was significantly higher (P<0.01). Apoptosis rate, Grp78, PERK, eIF2α, and p-c-JNK/JNK expression was also significantly decreased (P<0.01). Sevoflurane significantly reduced apoptosis and expression of PERK, eIF2α, p-c-JNK/JNK by inhibiting the expression of Grp78 (P<0.01). Conclusion: Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78.

Sign in / Sign up

Export Citation Format

Share Document