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ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure

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Hepatobiliary & Pancreatic Diseases International 2013年第2期12卷 180-188页

作者： Li-Kun Wang Lu-Wen Wang Xun Li Xiao-Qun Han Zuo-Jiong Gong Department of Infectious Diseases Renmin Hospita of Wuhan University

BACKGROUND: The pathogenesis and progression of acute liver failure (ALF) are closely associated with intestinal endotoxemia because of the high permeability of the intestinal wall. Treatment with ethyl pyruvate (EP) has been shown to protect liver failure effectively. The current study aimed to explore the relationship between proinflammatory cytokines and intestinal permeability, and to investigate whether EP administration might prevent the release of multiple proinflammatory cytokines and decrease intestinal permeability and therefore, protect the liver from injury. METHODS: The ALF model was induced by D-galactosamine in rats. The rats were randomly divided into control (saline i.p.), model (D-galactosamine, 1.2 g/kg, i.p.), prevention [EP injection (40 mg/kg) 2 hours ahead of D-galactosamine] and treatment groups (EP injection 2 hours after D-galactosamine) Samples were obtained at 12 and 24 hours after ALF induction respectively. The histology of liver and intestinal tissue was accessed. Serum alanine aminotransferase, endotoxin, D(-) lactate, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and high mobility group box-1 (HMGB1) were evaluated. The survival of rats was also recorded. RESULTS: The rats in model group showed severe damage to liver tissue and intestinal mucosa 12 and 24 hours after ALF induction. EP significantly improved liver or intestinal injury In addition, serum endotoxin, D(-)-lactate, DAO, TNF-α IFN-γ and HMGB1 levels were significantly increased in the model group compared with the control group. There was a positive correlation between intestinal permeability andproinflammatory cytokines. EP significantly reduced serum endotoxin, D(-)-lactate, DAO, TNF-α, IFN-γ and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group). CONCLUSIONS: EP has protective and therapeutic effects on intestinal mucos

关键词： acute liver failure ethyl pyruvate intestinal permeability cytokines

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Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

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World Journal of Gastroenterology 2008年第28期14卷 4546-4550页

作者： Zhi-Yong Yang Yan Ling Tao Yin Jing Tao Jiong-Xin Xiong He-Shui Wu Chun-You Wang Department of Pancreatic Surgery Xiehe Hospital Tongji Medical College Huazhong University of Sciecne and Technology Wuhan 430022 Hubei Province China

AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis （SAP）. METHODS： A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups （n = 32 in each group）： sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP （30 mg/kg） at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase （AST）, alanine arninotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） levels were measured. Lung wet-to-dry-weight （W/D） ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios （8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological scores （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 vs 1 368 ± 271, P 〈 0.01）, ALT （446 ± 91 vs 653 ± 98, P 〈 0.01） and Cr （1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01） levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h （P 〈 0.01）. CONCLUSION： Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome （MODS） in SAP patients.

关键词： Severe acute pancreatitis ethyl pyruvate High mobility group box 1 multiple organ dysfunction syndrome Survival time

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Effects of ethyl pyruvate on Myocardial Apoptosis and Expression of Bcl-2 and Bax Proteins after Ischemia-reperfusion in Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2008年第3期28卷 281-283页

作者：郭家龙张凯伦季艳梅蒋雄刚左顺庆 Department of Cardiovascular Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Intensive Care Unit Taihe Hospital Affiliated to Yunyang Medical College Department of Thoracic Surgery Taihe Hospital Affiliated to Yunyang Medical College

In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion （I/R） in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups （n=8 in each group）： control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. ethyl pyruvate （EP） group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 rain before ischemia and throughout reperfusion. Myocardial malonaldehyde （MDA） content was measured. Myocardial apoptotic index （AI） was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group （P〈0.05）. These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.

关键词： ethyl pyruvate myocardial reperfusion injury apoptosis Bcl-2 protein Bax protein

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ethyl pyruvate ameliorates the glial microenvironment and promotes spinal cord repair

Ethyl pyruvate ameliorates the glial microenvironment and pr...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yi-Min YUAN,Zhi-Da SU,Ying-Yan PU,Jing-Jing CHEN,Feng ZHU,Yang QIU,Cheng HE~* Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology,Second Military Medical University, Shanghai 200433,China

＜正＞Objective After SCI,a series of endogenous processes,including reactive astrogliosis and neuroinflammatory response,are triggered and resulted in the formation of a degenerative microenvironment in the lesion *** many studies,this hostile environment,as well as the intrinsic incapacity of the neuron to regenerate,is regarded as an important contributor to the failure of spontaneous anatomical and functional repair of *** present study is to explore the neuroprotective effect of ethyl pyruvate in the damaged spinal cord using a rat model of SCI. Methods Initially,a scratch-wound model was applied to test reactive astrogliosis in *** vivo,astrogliosis, scar formatting and neuroinflammatory response were further assessed with a spinal cord-hemisectined SCI model. In the damaged spinal cord,survival neurons and regenerative axons was identified by TUNEL staining and BDA anterograde tracing,***,functional recovery was valuated by the Basso,Beattie,and Bresnahan openfield scoring,grid-walk test and foot-print *** In the present study,ethyl pyruvate was found to inhibit reactive astrogliosis in vitro,which was further confirmed in injured spinal *** addition,ethyl pyruvate treatment was also shown to attenuate SCI-induced neuroinflammation by decreasing the Iba-1 or CD11b-positive inflammatory cells at the lesion ***,ethyl pyruvate-treated rats showed a significantly greater number of survival neurons and regenerative axons and their behavioral functions were evidently *** ethyl pyruvate ameliorates the glial microenvironment and promotes spinal cord repair,suggestive of a potent neuroprotective effect against SCI.

关键词： ethyl pyruvate astrogliosis neuroinflammation glial scar spinal cord injury axon regeneration

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Effects of ethyl pyruvate on High Mobility Group Box1 gene expression in septic lung of rat

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Journal of Nanjing Medical University 2005年第6期19卷 316-320页

作者： Lian Zeng Shanglong Yao Dong Liu Yuelan Wang Department of Anesthesiology Union Hospital Tongji Medical College Huazlmng Science and Technology University Wuhan 430022 China

Objective: ethyl pyruvate (EP) has been shown to be an effective anti-inflammatory agent in a variety of model systems. The aim of this study was to investigate the effects of EP on High Mobility Group Box1(HMGB1) genes expression and the possible mechanisms of EP protecting against acute lung injury induced by sepsis. Methods: Forty Wistar rats were randomly divided into normal controls,sham operation,acute lung injury,and EP treatment (40 mg/kg intra-peritoneally every 6 hrs) groups. At the time points of 24 hours the animals in each group were sacrificed, and the lungs were harvested. Wet/dry lung weight ratio, the protein in the bronchoalveolar lavage fluid(BALF),and pulmonary permeability index(PPI) were determined. The histological morphology of lung was observed under microscope. The expression of HMGB1 mRNA was measured using semi-quantitative RT-PCR. Results: EP treatment decreased wet/dry lung weight ratio, the protein in the BALF,and PPI (P<0.01). The histological morphology of lung injury was ameliorated. EP significantly inhibited the HMGB1 mRNA expression(P<0.01). HMGB1 mRNA expression in lungs positively correlation with wet/dry lung weight ratio, the protein in the BALF,and PPI. Conclusion: EP administered inhibits HMGB1 mRNA expression, and protects the lungs against acute injury induced by sepsis.

关键词： ethyl pyruvate acute lung injury High Mobility Group Boxl

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Efficient synthesis of functionalized butenolides mediated by vinyltriphenylphosphonium salts in aqueous media

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Chinese Chemical Letters 2011年第1期22卷 49-52页

作者： Mohammad A.Khalilzadeh Adel Hasannia Mohammad M.Baradarani Zinatossadat Hossaini Department of Chemistry Islamic Azad UniversityQaemshahr BranchMazandaranIran Department of Chemistry Faculty of ScienceUrmia UniversityUremiaIran

An efficient synthesis of 5-oxo-2,5-dihydro-3-furancarboxylate derivatives via reaction of dialkyl acetylenedicarboxylate with triphenylphosphine （Ph3P） in the presence of activated carbonyl compounds such as ethyl ... 详细信息

关键词： ethyl pyruvate Triphenylphosphine N-Alkylisatin Butenolides Dialkyl acetylenedicarboxylates

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A Convenient Method for the Preparation of 1,5-Diaryl-3-（arylamino）-I H-pyrrol-2（5 H）-ones

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Chinese Journal of Chemistry 2011年第9期29卷 1851-1855页

作者： Ghashang, Majid Shaterian, Hamid Reza~ Department of Chemistry Faculty of Sciences University of Sistan and Baluchestan PO Box 98135-674 Zahedan Iran

A simple and eco-friendly method for the preparation of 1,5-diaryl-3-（arylamino）-lH-pyrrol-2（5H）-ones via the cyclo-condensation reaction of aldehydes, amines and ethyl pyruvate in the presence of silica supported ferric chlo- ride （SiO2-FeCl3） as reusable heterogeneous catalyst is described. The present methodology offers several advantages such as excellent yields, simple procedure and short reaction times.

关键词： multicomponent reactions domino reactions SiO2-FeCl3 1,5-diaryl-3-(arylamino)-lH-pyrrol-2(5H)-one γ-lactam ethyl pyruvate

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