Optimal intervention time of ADSCs for hepatic ischemia-reperfusion combined with partial resection injury in rats

Objective: The present study was conducted to elucidate the underlying molecular mechanism as well as the potential hepatoprotective effects of royal jelly (RJ) against hepatic ischemia/reperfusion (IR) injury. Methods: Rats were assigned into four groups; sham (received vehicle), IR (30 minutes ischemia and 45 minutes reperfusion), sham pretreated with RJ (200 mg/kg P.O.), and IR pretreated with RJ (200 mg/kg P.O.). The experiment has lasted for 28 days. Results: Hepatic IR significantly induced hepatic dysfunctions, as manifested by elevation of serum transaminases, ALP and LDH levels. Moreover, hepatic IR caused a significant up-regulation of P38-MAPK, NF-κB-p65, TNF-α and MDA levels along with marked down-regulation of Nrf-2, HO-1, COX-4, cytoglobin, IκBa, IL-10, GSH, GST and SOD levels. Additionally, marked histopathological changes were observed after hepatic IR injury. On the contrary, pretreatment with RJ significantly improved hepatic functions along with the alleviation of histopathological changes. Moreover, RJ restored oxidant/antioxidant balance as well as hepatic expressions of Nrf-2, HO-1, COX-4, and cytoglobin. Simultaneously, RJ significantly mitigated the inflammatory response by down-regulation of P38-MAPK, NF-κB-p65, TNF-α expression. Conclusion: The present results revealed that RJ has successfully protected the liver against hepatic IR injury through modulation of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α signaling pathways.

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The role of microRNA in hepatic ischemia/reperfusion injury

MicroRNA ◽

10.2174/2211536609666200129162531 ◽

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.

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Inhibition of CKLF1 ameliorates hepatic ischemia-reperfusion injury via MAPK pathway

Cytokine ◽

10.1016/j.cyto.2021.155429 ◽

2021 ◽

Vol 141 ◽

pp. 155429

Author(s):

Fang-fang Li ◽

Xin Zhou ◽

Shi-feng Chu ◽

Nai-hong Chen

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Mapk Pathway ◽

Ischemia Reperfusion ◽

Hepatic Ischemia ◽

Hepatic Ischemia Reperfusion

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Hepatic ischemia reperfusion injury: effect of moderate intensity exercise and oxytocin compared to l-arginine in a rat model

Egyptian Liver Journal ◽

10.1186/s43066-021-00111-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Amr H. ELKady ◽

Bataa M. Elkafoury ◽

Dalia A. Saad ◽

Doaa M. Abd el-Wahed ◽

Walaa Baher ◽

...

Keyword(s):

Ischemia Reperfusion ◽

Serum Levels ◽

Treated Group ◽

Significant Decline ◽

Moderate Intensity ◽

Trained Group ◽

Moderate Intensity Exercise ◽

Hepatic Ischemia ◽

Tnf Α ◽

Hepatic Ischemia Reperfusion

Abstract Background Hepatic ischemia reperfusion (IR) injury is considered as a main cause of liver damage and dysfunction. The l-arginine/nitric oxide pathway seems to be relevant during this process of IR. Although acute intense exercise challenges the liver with increased reactive oxygen species (ROS), regular training improves hepatic antioxidant status. Also, oxytocin (Oxy), besides its classical functions, it exhibits a potent antistress, anti-inflammatory, and antioxidant effects. This study was designed to evaluate the hepatic functional and structural changes induced by hepatic IR injury in rats and to probe the effect and potential mechanism of moderate intensity exercise training and/or Oxy, in comparison to a nitric oxide donor, l-arginine, against liver IR-induced damage. Results Compared to the sham-operated control group, the hepatic IR group displayed a significant increase in serum levels of ALT and AST, plasma levels of MDA and TNF-α, and significant decrease in plasma TAC and nitrite levels together with the worsening of liver histological picture. L-Arg, Oxy, moderate intensity exercise, and the combination of both Oxy and moderate intensity exercises ameliorated these deleterious effects that were evident by the significant decrease in serum levels of ALT and AST, significant elevation in TAC and nitrite, and significant decline in lipid peroxidation (MDA) and TNF-α, besides regression of histopathological score regarding hepatocyte necrosis, vacuolization, and nuclear pyknosis. Both the moderate intensity exercise-trained group and Oxy-treated group showed a significant decline in TNF-α and nitrite levels as compared to l-Arg-treated group. The Oxy-treated group showed statistical insignificant changes in serum levels of ALT, AST, and plasma levels of nitrite, MDA, TAC, and TNF-α as compared to moderate intensity exercise-trained group. Conclusion The combination of both moderate intensity exercise and Oxy displayed more pronounced hepatoprotection on comparison with l-Arg which could be attributed to their more prominent antioxidant and anti-inflammatory effects but not due to their NO-enhancing effect.

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N6-methyladenosine demethylase FTO impairs hepatic ischemia–reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation

Cell Death and Disease ◽

10.1038/s41419-021-03622-x ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Ying Dong Du ◽

Wen Yuan Guo ◽

Cong Hui Han ◽

Ying Wang ◽

Xiao Song Chen ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mitochondrial Fragmentation ◽

Hepatic Ischemia ◽

Adeno Associated Virus ◽

Downstream Target ◽

Hepatic Ischemia Reperfusion

AbstractDespite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia–reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.

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