scholarly journals Galangin Alleviates Liver Ischemia-Reperfusion Injury in a Rat Model by Mediating the PI3K/AKT Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1354-1363 ◽  
Author(s):  
Yang Li ◽  
Liquan Tong ◽  
Jingyan Zhang ◽  
Yafeng Zhang ◽  
Feng  Zhang
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Hepatic Duct ◽  
Ischemia Reperfusion ◽  
Trauma Surgery ◽  
Liver Ischemia ◽  
Western Blots ◽  
Phosphorylated Akt ◽  
Related Proteins

Background/Aims: Liver ischemia-reperfusion (I/R) injury is a pathological process that often occurs during liver and trauma surgery. There are numerous causes of liver I/R injury, but the mechanism is unknown. Galangin (GA) is a flavonoid, a polyphenolic compound widely distributed in medicinal herbs that has anti-inflammatory, antioxidant, and antitumor activity. This study evaluated the protective effect of GA on hepatic I/R injury. Methods: An I/R model was created in male Wistar rats by clamping the hepatoportal vein, hepatic artery and hepatic duct for 30 min followed by reperfusion for 2 h. A hypoxia/restoration (H/R) model was established in buffalo rat liver (BRL) cells by hypoxia for 4 h followed by normoxic conditions for 10 h. The extent of liver injury was assayed by serum ALT/AST, hepatic histology, and MPO activity. Oxidative stress was assayed by serum superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA). Expression of apoptosis-related proteins in BRL cells was assayed in western blots. Expression of AKT and p-AKT proteins in vivo and vitro were assayed in western blots. Results: GA significantly decreased ALT/AST expression, reversed changes in oxidative stress markers induced by I/R, and mediated caspase-3 activity expression of apoptosis-related proteins in vivo and in vitro. Methylthiazol tetrazolium (MTT) assay, flow cytometry, and Hoechst 33258 staining confirmed that GA inhibited apoptosis of BRL cells. GA also increased the expression of phosphorylated AKT after H/R. Conclusion: GA reduced liver I/R injury both in vivo and vitro and inhibited BRL cell apoptosis. PI3K/AKT signaling have been involved. GA may protect against liver I/R and be a potential therapeutic candidate.

scholarly journals Renalase Attenuates Mouse Fatty Liver Ischemia/Reperfusion Injury through Mitigating Oxidative Stress and Mitochondrial Damage via Activating SIRT1

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Tao Zhang ◽  
Jian Gu ◽  
Jianrong Guo ◽  
Ke Chen ◽  
Huili Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Diet ◽  
Liver Ischemia ◽  
Portal Triad ◽  
Nonalcoholic Fatty Liver

Liver ischemia/reperfusion (IR) injury is a severe complication of liver surgery. Moreover, nonalcoholic fatty liver disease (NAFLD) patients are particularly vulnerable to IR injury, with higher rates of postoperative morbidity and mortality after liver surgeries. Our previous study found that renalase (RNLS) was highly sensitive and responsive to oxidative stress, which may be a promising biomarker for the evaluation of the severity of liver IR injury. However, the role of RNLS in liver IR injury remains unclear. In the present study, we intensively explored the role and mechanism of RNLS in fatty liver IR injury in vivo and in vitro. C57BL/6 mice were divided into 2 groups feeding with high-fat diet (HFD) and control diet (CD), respectively. After 20 weeks’ feeding, they were suffered from portal triad blockage and reflow to induce liver IR injury. Additionally, oleic acid (OA) and tert-butyl hydroperoxide (t-BHP) were used in vitro to induce steatotic hepatocytes and to simulate ROS burst and mimic cellular oxidative stress following portal triad blockage and reflow, respectively. Our data showed that RNLS was downregulated in fatty livers, and RNLS administration effectively attenuated IR injury by reducing ROS production and improving mitochondrial function through activating SIRT1. Additionally, the downregulation of RNLS in the fatty liver was mediated by a decrease of signal transduction and activator of transcription 3 (STAT3) expression under HFD conditions. These findings make RNLS a promising therapeutic strategy for the attenuation of liver IR injury.

In vivo and In vitro PPAR-y Activation Decreases M1-Macrophage Polarization and Improves Liver Ischemia Reperfusion Injury

2018 ◽  
Vol 102 ◽  
pp. S708
Author(s):  
Ivan Linares ◽  
Agata Bartczak ◽  
Kaveh Farrokhi ◽  
Dagmar Kollmann ◽  
Moritz Kaths ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Macrophage Polarization ◽  
Liver Ischemia ◽  
M1 Macrophage

Abstract 10246: Hydroxychloroquine Pretreatment Reduces Myocardial Ischemia-Reperfusion Injury: Role of Cardiac Extracellular-Signal-Regulated Kinase 5 and Autophagy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Feiyan Yang ◽  
Chang Yin ◽  
Lei Xi ◽  
Rakesh C Kukreja
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Beclin 1 ◽  
Myocardial Infarct Size ◽  
Western Blots ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Related Proteins

Background: Hydroxychloroquine (HCQ) is an antimalarial drug, which is also widely used to treat chronic rheumatologic diseases. Since HCQ was reported to inhibit cell autophagy and to activate extracellular-signal-regulated kinase 5 (ERK5) in vascular endothelial cells, we designed the current study to determine the effects of HCQ on cardiac ischemia-reperfusion (I-R) injury and post-I-R expression of ERK5 and autophagy marker proteins. Methods: Adult C57BL/6J mice of both genders were pretreated with HCQ (50 mg/kg, i.p.) 1 hour prior to isolation of the hearts, which were subjected to 30 min of no-flow global ischemia followed by 60 min of reperfusion in Langendorff mode. Ventricular function was continuously assessed and myocardial infarct size was determined at the end of I-R. Heart samples were collected following normoxic perfusion (no-ischemic controls), I-R, or I-R with HCQ for assessing ERK5 and autophagy-related proteins with Western blots. Results: HCQ pretreatment reduced infarct size significantly in the female hearts (P<0.05) as compared with the male hearts (Fig. A). Post-I-R cardiac function was better in HCQ-treated males (Fig. B). I-R resulted in a robust increase in total ERK5 (Fig. C) and phosphorylated ERK5 (Thr218/Tyr220) in both genders, which was abolished in HCQ-treated groups. Conversely, either I-R or HCQ did not affect the post-I-R cardiac expression of autophagy-related proteins (e.g., Atg5, Beclin-1, LC3II/LC3I ratio), except Beclin-1 phosphorylation was inhibited in HCQ-treated male hearts, but not females (Fig. D). Conclusions: Acute HCQ pretreatment affords cardioprotection against I-R injury in both genders. Interestingly, cardioprotective effects of HCQ are associated with a strong inhibitory effect on the induction of ERK5 following I-R in the heart, indicating a novel molecular mechanism underlying the HCQ-induced cardioprotection. However, the cardioprotective dose of HCQ has no major impact on cardiac autophagy.

scholarly journals Mangiferin Attenuates Myocardial Ischemia-Reperfusion Injury via MAPK/Nrf-2/HO-1/NF-κB In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Kun Liu ◽  
Fei Wang ◽  
Shuo Wang ◽  
Wei-Nan Li ◽  
Qing Ye
Keyword(s):  
Oxidative Stress ◽  
Coronary Artery ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cells ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

The aim of this study was to investigate the cardioprotective effect of mangiferin (MAF) in vitro and in vivo. Oxidative stress and inflammatory injury were detected in coronary artery ligation in rats and also in hypoxia-reoxygenation- (H/R-) induced H9c2 cells. MAF inhibited myocardial oxidative stress and proinflammatory cytokines in rats with coronary artery occlusion. The ST segment of MAF treatment groups also resumed. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that MAF could significantly reduce myocardial injury. In vitro data showed that MAF could improve hypoxia/reoxygenation- (H/R-) induced H9c2 cell activity. In addition, MAF could significantly reduce oxidative stress and inflammatory pathway protein expression in H/R-induced H9c2 cells. This study has clarified the protective effects of MAF on myocardial injury and also confirmed that oxidative stress and inflammation were involved in the myocardial ischemia-reperfusion injury (I/R) model.

scholarly journals PRELIMINARY RESULTS OF TOPICAL HEPATIC HYPOTHERMIA IN A MODEL OF LIVER ISCHEMIA/REPERFUSION INJURY IN RATS

2017 ◽  
Vol 54 (3) ◽  
pp. 246-249 ◽  
Author(s):  
Emilio Elias ABDO ◽  
Estela Regina Ramos FIGUEIRA ◽  
Joel Avancini ROCHA-FILHO ◽  
Eleazar CHAIB ◽  
Luiz Augusto Carneiro D’ALBUQUERQUE ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxygen Demand ◽  
Practical Method ◽  
Liver Ischemia ◽  
Liver Preservation ◽  
Normothermic Group ◽  
Hypothermic Group

ABSTRACT BACKGROUND Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. OBJECTIVE: To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. METHODS We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. RESULTS The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. CONCLUSION: A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.

scholarly journals The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

2016 ◽  
Vol 38 (4) ◽  
pp. 1631-1642 ◽  
Author(s):  
Zhijie Xu ◽  
Jingui Yu ◽  
Jianbo Wu ◽  
Feng Qi ◽  
Huanliang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Group ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Ischemia ◽  
Hepatic Ischemia ◽  
Group I ◽  
Hepatic Ischemia Reperfusion

Background: Propofol and sevoflurane are widely used in clinical anesthesia, and both have been reported to exert a protective effect in organ ischemia/reperfusion (IR). This study aims to investigate and compare the effects of propofol and sevoflurane on liver ischemia/reperfusion and the precise molecular mechanism. Methods and Materials: Rats were randomized into four groups: the sham group, I/R group, propofol treatment group (infused with 1% propofol at 500 µg· kg-1· min-1), and sevoflurane treatment group (infused with 3% (2 L/min) sevoflurane). The liver ischemia/reperfusion model was used to evaluate the hepatoprotective effect on ischemic injury. Liver enzyme leakage, liver cytokines and histopathological examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. Oxidative stress was investigated by evaluating the levels of Malondialdehyde(MDA), Superoxide Dismutase(SOD) and NO. The terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay and western blot were applied to detect apoptosis in the ischemic liver tissue and its mechanism. Results: Both propofol and sevoflurane attenuated the extent of hepatic ischemia/reperfusion injury which is evident from the hisopathological studies and alterations in liver enzymes such as AST and LDH by inhibiting Nuclear factor kappa B (NFκB) activation and subsequent alterations in inflammatory cytokines interleukin-1(IL-1), interleukin-6(IL-6), tumor necrosis factor-alpha (TNF-a) and increased IL10 release. Propofol exhibited a similar protective effect and a lower IL-1 release, while sevoflurane decreased TNF-a leakage more significantly. Meanwhile, oxidative stress was attenuated by reduced MDA and NO and elevated SOD release. The expression of antiapoptotic protein Bcl-2 and Bcl-xl were enhanced while that of apoptotic protein Bax and Bak were reduced by both propofol and sevoflurane to regulate hepatic apoptosis. In addition, propofol downregulated the phosphorylation of AKT and Bad protein, while sevoflurane downregulated the phosphorylation of p38. In addition, Both the treatments had no effect on the expression of AKT, Bad and p38. Conclusion: Both propofol and sevoflurane can protect the liver from ischemia/reperfusion injury by modulating the inflammatory responses reducing oxidative stress and liver apoptosis.

scholarly journals Nrf2 and Oxidative Stress in liver Ischemia/Reperfusion Injury

FEBS Journal ◽  
2021 ◽  
Author(s):  
Raquel G. Bardallo ◽  
Arnau Panisello‐Roselló ◽  
Sergio Sanchez‐Nuno ◽  
Norma Alva ◽  
Joan Roselló‐Catafau ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Ischemia ◽  
And Oxidative Stress

scholarly journals Targeted Delivery of Intranasally Administered Cyclovirobuxine D Liposomes to Brain for Treatment Cerebral Ischemia-Reperfusion Injury via Anti-oxidative Stress and Activating Autophagy

2022 ◽  
Author(s):  
Tuo Liu ◽  
Fang Yang ◽  
Xiangyi Lu ◽  
Chang Liu ◽  
Yang Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Protein Expressions ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Ht22 Cell

Abstract The lack of effective therapy mandates development of treatment for cerebral ischemia-reperfusion injury (CIRI. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study focused on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. In order to evaluate these, the CIRI rat model was induced by middle cerebral artery occlusion (MCAO)-reperfusion. Pharmacological evaluation was assessed in vivo by general indexs, neurobehavioral scores, triphenyl tetrazolium chloride (TTC) staining, histopathological staining (HE staining and Nissl staining), small animal magnetic resonance imaging, biochemical assay and Western blot. The results show that CVBD liposomes alleviated pathological damage of brain. Futhermore, the protective effect of CVBD liposomes on OGD/R-injured HT22 cell was investigated by cell fusion degree, cell proliferation curve and cell viability. OGD/R-injured HT22 cell was infected by mRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were observed by laser confocal microscopy, and autophagy-related protein expressions (LC3, p62 and Beclin 1) were analyzed by Western blot. Meanwhile, the classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulated mechanism of CVBD brain-targeted liposomes in treating CIRI. In cell model of oxygen and glucose deprivation/re-oxygenation, CVBD liposomes increased cell viability and decreased ROS level. CVBD liposomes improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated to anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro, showing a great potential in treating CIRI in clinic.

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