Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers

Cannistrà, Marco; Ruggiero, Michele; Zullo, Alessandra; Gallelli, Giuseppe; Serafini, Simone; Mazzitelli, Maria; Naso, Agostino; Grande, Raffaele; Serra, Raffaele; Nardo, Bruno

doi:10.1016/j.ijsu.2016.05.050

Cited by 269 publications

(255 citation statements)

References 217 publications

Supporting

Mentioning

231

Contrasting

Unclassified

Order By: Relevance

“…Sub-acute inflammatory responses have been demonstrated to lead to the progression of liver damage during hepatic I/R injury through the release of proinflammatory cytokines and accumulation of neutrophils, which secrete oxidants and proteases [32]. However, approaches to reduce inflammation in hepatic I/R injury are still lacking.…”

Section: Discussionmentioning

confidence: 99%

Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling

Xu¹,

Zhu²,

Jeong³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The role of Rictor in hepatic ischemia/reperfusion (I/R) injury remains unknown. Here, we comprehensively examined the role of Rictor in hepatic I/R injury. Methods: We studied the expression of Rictor during hepatic I/R injury. The regulatory effects of Rictor on inflammatory responses, cytokine and chemokine release, apoptotic and anti-apoptotic responses, and autophagy induction during hepatic I/R injury were identified via the shRNA-mediated knockdown of Rictor. Subsequently, we collected the liver and blood samples of these mice to evaluate liver injury, mRNA and protein levels. Additionally, the signaling pathways induced by Rictor were investigated. Furthermore, the extent of activation of MAPKs in response to Rictor deficiency was investigated in lipopolysaccharide (LPS)-treated RAW264.7 cells. The mRNA expression levels were analyzed by real-time PCR, and the protein expression levels were analyzed using Western blot, immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Results: The expression of Rictor was increased during hepatic I/R injury in vivo and hypoxia/reoxygenation (H/R) injury in vitro. Rictor deficiency enhanced the extent of liver injury by increasing macrophage and neutrophil infiltration, promoting cytokine and chemokine release, aggravating hepatocyte apoptosis, suppressing anti-apoptotic responses, and inhibiting autophagy induction during both hepatic I/R and H/R injury. Rictor was associated with the activation of hepatic I/R injury-induced MAPK signaling. In addition, Rictor deficiency affected MAPK activation in LPS-treated RAW264.7 cells. Conclusion: Rictor can substantially ameliorate I/R-induced liver injury. Therefore, our findings strongly suggest a therapeutic value of the Rictor/mTORC2 axis in hepatic I/R injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling

Xu¹,

Zhu²,

Jeong³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Using free radical scavengers to limit IRI in liver transplantation is an elegant idea that unfortunately has not been clinically effective. Much effort has focused on the use of N‐acetyl‐cysteine (NAC), a glutathione precursor, as a free radical scavenger . NAC use in acetaminophen overdose has shown promise, but its effectiveness in liver transplantation is less clear .…”

Section: Therapeutics For Hepatic Irimentioning

confidence: 99%

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Dar

Sullivan

Bynon

et al. 2019

Liver International

261

245

View full text Add to dashboard Cite

Liver disease causing end organ failure is a growing cause of mortality. In most cases, the only therapy is liver transplantation. However, liver transplantation is a complex undertaking and its success is dependent on a number of factors. In particular, liver transplantation is subject to the risks of ischaemia‐reperfusion injury (IRI). Liver IRI has significant effects on the function of a liver after transplantation. The cellular and molecular mechanisms governing IRI in liver transplantation are numerous. They involve multiple cells types such as liver sinusoidal endothelial cells, hepatocytes, Kupffer cells, neutrophils and platelets acting via an interconnected network of molecular pathways such as activation of toll‐like receptor signalling, alterations in micro‐RNA expression, production of ROS, regulation of autophagy and activation of hypoxia‐inducible factors. Interestingly, the cellular and molecular events in liver IRI can be correlated with clinical risk factors for IRI in liver transplantation such as donor organ steatosis, ischaemic times, donor age, and donor and recipient coagulopathy. Thus, understanding the relationship of the clinical risk factors for liver IRI to the cellular and molecular mechanisms that govern it is critical to higher levels of success after liver transplantation. This in turn will help in the discovery of therapeutics for IRI in liver transplantation – a process that will lead to improved outcomes for patients suffering from end‐stage liver disease.

show abstract

“…Following the historical AF observations mentioned above on the yellowish, highly fluorescing material in cirrhotic livers, lipofuscins and lipofuscin‐like products in the liver parenchyma have recently regained attention as biomarkers of oxidative metabolic disorders. In fact, oxidative stress can favour disease progression or increase the risk of injury and functional impairment of normal and fatty livers faced with ischaemia and reperfusion in surgery and transplantation . The peroxidation of lipids has long been measured biochemically in terms of malondialdehyde, a thiobarbituric acid reactive substance (TBARS) .…”

Section: Optical Biopsy In Hepatologymentioning

confidence: 99%

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Croce

Ferrigno

Bottiroli

et al. 2018

Liver International

View full text Add to dashboard Cite

Autofluorescence emission of liver tissue depends on the presence of endogenous biomolecules able to fluoresce under suitable light excitation. Overall autofluorescence emission contains much information of diagnostic value because it is the sum of individual autofluorescence contributions from fluorophores involved in metabolism, for example, NAD(P)H, flavins, lipofuscins, retinoids, porphyrins, bilirubin and lipids, or in structural architecture, for example, fibrous proteins, in close relationship with normal, altered or diseased conditions of the liver. Since the 1950s, hepatocytes and liver have been historical models to study NAD(P)H and flavins as in situ, real-time autofluorescence biomarkers of energy metabolism and redox state. Later investigations designed to monitor organ responses to ischaemia/reperfusion were able to predict the risk of dysfunction in surgery and transplantation or support the development of procedures to ameliorate the liver outcome. Subsequently, fluorescent fatty acids, lipofuscin-like lipopigments and collagen were characterized as optical biomarkers of liver steatosis, oxidative stress damage, fibrosis and disease progression. Currently, serum AF is being investigated to improve non-invasive optical diagnosis of liver disease. Validation of endogenous fluorophores and in situ discrimination of cancerous from non-cancerous tissue belong to the few studies on liver in human subjects. These reports along with other optical techniques and the huge work performed on animal models suggest many optically based applications in hepatology. Optical diagnosis is currently offering beneficial outcomes in clinical fields ranging from the respiratory and gastrointestinal tracts, to dermatology and ophthalmology. Accordingly, this review aims to promote an effective bench to bedside transfer in hepatology.

show abstract

Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers

Cited by 269 publications

References 217 publications

Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling

Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Contact Info

Product

Resources

About