Protective effects of hydroxytyrosol on liver ischemia/reperfusion injury in mice

Pan, Shangha; Liu, Lianxin; Pan, Huayang; Ma, Yong; Wang, Dawei; Kang, Kai; Wang, Jizhou; Sun, Bei; Sun, Xueying; Jiang, Hongchi

doi:10.1002/mnfr.201300010

Cited by 52 publications

(46 citation statements)

References 33 publications

(58 reference statements)

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“…It has been demonstrated that the activation of Kupffer cells, production of cytokines, cell adhesion factor, and reactive oxygen species (ROS) play a pivotal role in the pathogenesis of hepatic I/R injury [6, 7]. The main pathological changes of hepatic I/R injury are the neutrophil infiltration and liver cell death caused by diverse factors.…”

Section: Introductionmentioning

confidence: 99%

Ethyl Pyruvate Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Intrinsic Pathway of Apoptosis and Autophagy

Miao

Lü

Dai

et al. 2013

Mediators of Inflammation

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Background. Hepatic ischemia-reperfusion (I/R) injury is a pivotal clinical problem occurring in many clinical conditions such as transplantation, trauma, and hepatic failure after hemorrhagic shock. Apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. Ethyl pyruvate, a stable and simple lipophilic ester, has been shown to have anti-inflammatory properties. In this study, the purpose is to explore both the effect of ethyl pyruvate on hepatic I/R injury and regulation of intrinsic pathway of apoptosis and autophagy. Methods. Three doses of ethyl pyruvate (20 mg/kg, 40 mg/kg, and 80 mg/kg) were administered 1 h before a model of segmental (70%) hepatic warm ischemia was established in Balb/c mice. All serum and liver tissues were obtained at three different time points (4 h, 8 h, and 16 h). Results. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and pathological features were significantly ameliorated by ethyl pyruvate (80 mg/kg). The expression of Bcl-2, Bax, Beclin-1, and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, was also obviously decreased by ethyl pyruvate (80 mg/kg). Furthermore, ethyl pyruvate inhibited the HMGB1/TLR4/ NF-κb axis and the release of cytokines (TNF-α and IL-6). Conclusion. Our results showed that ethyl pyruvate might attenuate to hepatic I/R injury by inhibiting intrinsic pathway of apoptosis and autophagy, mediated partly through downregulation of HMGB1/TLR4/ NF-κb axis and the competitive interaction with Beclin-1 of HMGB1.

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Section: Introductionmentioning

confidence: 99%

Ethyl Pyruvate Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Intrinsic Pathway of Apoptosis and Autophagy

Miao

Lü

Dai

et al. 2013

Mediators of Inflammation

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“…Previous studies have demonstrated that PF is able to increase SOD levels in ischemic brain tissue, and reduce MDA content (27). In addItion, it has been suggested that PF inhibits the production of free radicals, improves SOD activity in the brain, and decreases MDA content following cerebral ischemia; therefore protecting secondary neurons from injury (15,28,29). PF has a strong anti-inflammatory effect, which has been shown to reduce the enhanced phagocytic function of peritoneal macrophages in rheumatoid arthritis models, and lower levels of TNF-α, IL-1 and IL-6 (30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin attenuates hepatic ischemia/reperfusion injury via anti-oxidative, anti-inflammatory and anti-apoptotic pathways

Tao

Wen

Song

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. During liver surgery, hepatic blood flow needs to be blocked in order to reduce bleeding, which inevitably results in hepatic ischemia/reperfusion injury (HI/R). Paeoniflorin (PF) is the main active ingredient of the traditional Chinese herbal medicine peony, which has been shown to exert anti-oxidative and anti-apoptotic properties. In the present study, a mouse model of HI/R was generated by clamping the hepatoportal vein, hepatic artery, and hepatic duct of BALB/c mice with a vascular clamp for 30 min, followed by reperfusion for 6 h under anesthesia. Six mice in the three PF treatment groups (5, 10 and 20 mg/kg) were then injected with PF, via the tail vein. A sham group, consisting of six mice that did not undergo the procedure, and a vehicle group, consisting of 6 mice that underwent the procedure but subsequently received injections of physiological saline only, were used as controls. Liver injury was indicated by serum levels of the enzymes alanine transaminase (ALT) and aspartate transaminase (AST). The activities of oxidative stress biomarkers, including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA), were also measured. Furthermore, the activity of caspase-3 was analyzed in hepatic tissue using a commercial kit. Treatment with PF significantly attenuated HI/R injury histologically, as compared with the vehicle group. In addition, significant reductions in the serum levels of ALT and AST were observed in the PF-treated ischemic mice. Furthermore, treatment with PF enhanced the activities of hepatic tissue SOD, GSH and GSH-PX, but decreased the MDA content. Treatment of ischemic mice with PF markedly reduced the expression levels of inflammatory mediators, including nuclear factor-κB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, and decreased the HI/R injury-induced expression of caspase-3. The results of the present study suggest that PF attenuates the HI/R injury of mice via anti-oxidative, anti-inflammatory and anti-apoptotic activities.

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“…A similar study with ambroxol, proved its protective action against hepatic IR injury via attenuation of JNK activation and lowering of Bax, Bcl‐2 and caspase‐3 expressions . Likewise, hydroxytyrosol, a phenolic compound from the olive oil has been shown to execute its sentinel role against hepatic IR, by lowering the levels of TNF‐α, IL‐6, macrophage inflammatory protein‐2 and inhibiting the ROS‐ induced oxidative damage in liver . Huperizine A, an alkaloid from Huperzia serratia , a widely used plant in chinese traditional medicine has been reported to exert anti‐apoptotic role through down regulation of Bax/Bcl2 ratio, and caspase‐3expression in rat model of hepatic IR with portal and bile duct clamping …”

Section: Introductionmentioning

confidence: 84%

Preconditioning methods in the management of hepatic ischemia reperfusion‐ induced injury: Update on molecular and future perspectives

Arumugam

Thirunavukkarasu

2016

Hepatology Research

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Hepatic IR (ischemia reperfusion) injury is a commonly encountered obstacle in the post-operative management of hepatic surgery. Hepatic IR occurs during 'Pringle maneuver' for reduction of blood loss or during a brief period of cold storage followed by reperfusion of liver grafts. The stress induced during hepatic IR, triggers a spectrum of cellular responses leading to the varying degrees of hepatic complications which in turn affect the post operative care. Different preconditioning methods either activate or subdue different sets of molecular signals, resulting in varied levels of protection against hepatic IR injury. Yet, there is a serious lacuna in the knowledge regarding the choice of preconditioning methods and the resulting molecular changes in order to assess the efficiency and choice of these methods correctly. This review provides an update on the various preconditioning approaches such as surgical/ischemic, antioxidant, pharmaceutical and genetic preconditioning strategies published during last six years (2009-2015). Further, we discuss the attenuation or inhibition of specific inflammatory, apoptotic and necrotic markers in the various experimental models of liver IR subjected to different preconditioning strategies. While enlisting the controversies in the ischemic preconditioning strategy, we bring out the uncertainties in the existing molecular targets and their reliability in the attenuation of hepatic IR injury. Future research studies would include the novel preconditioning strategies employ i) the targeted gene silencing of key molecular targets inducing IR, ii) hyper expression of beneficial molecular signals against IR via gene transfer techniques. The above studies would see the combination of these latest techniques with the established preconditioning strategies for better post-operative hepatic management.

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Protective effects of hydroxytyrosol on liver ischemia/reperfusion injury in mice

Abstract: HT exerts protective effects against hepatic I/R injury in mice, which might be associated with its anti-oxidative, anti-inflammatory, and anti-apoptotic properties. HT may be an effective hepatoprotective agent and a promising candidate for the treatment of liver I/R injury.

Cited by 52 publications

References 33 publications

Ethyl Pyruvate Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Intrinsic Pathway of Apoptosis and Autophagy

Ethyl Pyruvate Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Intrinsic Pathway of Apoptosis and Autophagy

Paeoniflorin attenuates hepatic ischemia/reperfusion injury via anti-oxidative, anti-inflammatory and anti-apoptotic pathways

Preconditioning methods in the management of hepatic ischemia reperfusion‐ induced injury: Update on molecular and future perspectives

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