Biochanin A attenuates spinal cord injury in rats during early stages by inhibiting oxidative stress and inflammasome activation

Previous studies have shown that Biochanin A,a flavonoid compound with estrogenic effects,can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury;howeve r,its effect on spinal cord injury is still unclea r. In this study,a rat model of spinal cord injury was established using the heavy o bject impact method,and the rats were then treated with Biochanin A(40 mg/kg) via intrape ritoneal injection for 14 consecutive days.The res ults showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal co rd tissue injury,reduced inflammation and oxidative stress in spinal cord neuro ns,and reduced apoptosis and pyroptosis.In addition,Biochanin A inhibited the expression of inflammasome-related proteins(ASC,NLRP3,and GSDMD)and the Toll-like receptor 4/nuclear factor-κB pathway,activated the Nrf2/heme oxygenase 1 signaling pathway,and increased the expression of the autophagy markers LC3 Ⅱ,Beclin-1,and P62.Moreove r,the therapeutic effects of Biochanin A on early post-s pinal cord injury were similar to those of methylprednisolone.These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways.These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

Lactobacillus plantarum AR113 attenuates liver injury in D-galactose-induced aging mice via the inhibition of oxidative stress and endoplasmic reticulum stress

Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.

Protective effect of camellia oil on H_(2)O_(2)-induced oxidative stress injury in H9C2 cardiomyocytes of rats

Objective: To explore the protective effect of camellia oil against H2O2-induced oxidative stress injury in rat H9C2 cardiomyocytes. Methods: CCK8 method was used to detect the cell survival rate of H9C2 cardiomyocytes treated with different concentrations of H2O2. Normal cultured cells were used as the blank control group, and the cells were treated with 200 μmol/L H2O2 for 24 h. An oxidative stress injury model was constructed as the model group. The cells were pretreated with 1%, 0.1% and 0.01% camellia oil for 24 h, and then H2O2 was added for 24 h as the experimental group. The β-galactosidase senescence staining assay, mitochondrial membrane potential assay, EdU cell proliferation staining assay and scratch assay were used to observe the changes of cell senescence, mitochondrial membrane potential, proliferation, apoptosis and migration in each group. The superoxide dismutase (SOD) activity, lactate dehydrogenase (LDH) activity, and malondialdehyde (MDA) content of the cells in each group were detected by using the kit. Results: The cell viability of H9C2 cardiomyocytes treated with different concentrations of H2O2 was inhibited and positively correlated with the concentration of H2O2 (P<0.01). Compared with the blank control group, the positive rate of cell senescence, MDA content and LDH activity increased in the H2O2 model group (P<0.01);mitochondrial membrane potential, cellular value-added rate, migration rate and SOD activity decreased (P<0.01). Compared with the H2O2 model group, the positive rate of cellular senescence (P<0.01 or P<0.05), MDA content and LDH activity decreased (P< 0.01 or P<0.05);mitochondrial membrane potential increased, cell proliferation rate and migration rate increased (P<0.01 or P<0.05) in the experimental group. Conclusion: Camellia oil can significantly inhibit oxidative stress injury in H9C2 cells and exert cardiomyocyte protective effects.

Inhibiting tau protein improves the recovery of spinal cord injury in rats by alleviating neuroinflammation and oxidative stress

After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.

Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation

Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional recovery of the injured CNS.Methods:A compressive SCI mouse model was utilized for this investigation.Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein,acrolein-induced inflammation-related factors,and macrophages at the injury site and within the CNS.Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase(PI3K)/AKT pathway to study macrophage regulation.The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67(GAD65/67),vesicular glutamate transporter 1(VGLUT1),paw withdrawal response,and Basso Mouse Scale score.Nissl staining and Luxol Fast Blue(LFB)staining were performed to investigate the structural recovery of the injured CNS.Results:Hydralazine downregulated the levels of acrolein,IL-1β,and TNF-αin the spinal cord.The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway,leading to M2 macrophage polarization,which protected neurons against SCI-induced inflammation.Additionally,hydralazine promoted the structural recovery of the injured spinal cord area.Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression.Furthermore,hydralazine facilitated motor function recovery following SCI.Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.Conclusion:Hydralazine,an acrolein scavenger,significantly mitigated SCI-induced inflammation and oxidative stress in vivo,modulated macrophage activation,and consequently promoted the structural and functional recovery of the injured CNS.

Lycium barbarum polysaccharides protects retinal ganglion cells against oxidative stress injury

The accumulation of excessive reactive oxygen species can exacerbate any injury of retinal tissue because free radicals can trigger lipid peroxidation,protein damage and DNA fragmentation.Increased oxidative stress is associated with the common pathological process of many eye diseases,such as glaucoma,diabetic retinopathy and ischemic optic neuropathy.Many studies have demonstrated that Lycium barbarum polysaccharides(LBP)protects against oxidative injury in numerous cells and tissues.For the model of hypoxia we used cultured retinal ganglion cells and induced hypoxia by incubating with 200μM cobalt chloride(CoCl2)for 24 hours.To investigate the protective effect of LBP and its mechanism of action against oxidative stress injury,the retinal tissue was pretreated with 0.5 mg/mL LBP for 24 hours.The results of flow cytometric analysis showed LBP could effectively reduce the CoCl2-induced retinal ganglion cell apoptosis,inhibited the generation of reactive oxygen species and the reduction of mitochondrial membrane potential.These findings suggested that LBP could protect retinal ganglion cells from CoCl2-induced apoptosis by reducing mitochondrial membrane potential and reactive oxygen species.

Abdominal paracentesis drainage ameliorates myocardial injury in severe experimental pancreatitis rats through suppressing oxidative stress

BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms.METHODS SAP was induced by 5%sodium taurocholate retrograde injection in Sprague-Dawley rats.APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction.Morphological staining,serum amylase and inflammatory mediators,serum and ascites high mobility group box(HMGB)1,cardiac-related enzymes indexes and cardiac function,oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats.Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined.RESULTS APD treatment improved cardiac morphological changes,inhibited cardiac dysfunction,decreased cardiac enzymes and reduced cardiomyocyte apoptosis,proapoptotic Bax and cleaved caspase-3 protein levels.APD significantly decreased serum levels of HMGB1,inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury.Furthermore,the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.CONCLUSION APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress,which may be a novel mechanism behind the effectiveness of APD on SAP.

Melatonin reduces traumatic brain injury-induced oxidative stress in the cerebral cortex and blood of rats

Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We in-vestigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vita-min E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain inju-ry-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.

Chrysanthemum extract alleviates acetaminophen-induced liver injury by inhibiting oxidative stress via AMPK pathway in rats

OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP to fight diseases but have also suffered the adverse effects brought about by APAP for more than half a cen⁃tury.The most serious adverse reaction to APAP is hepatotoxicity caused by overdose or long-term use.In Chinese tra⁃ditional medicine,chrysanthemums have the functions of dispelling wind,dissipating heat,clearing the liver and improv⁃ing eyesight.Although the chrysanthemum variety named Bianliang ziyu from Kaifeng is not a medicinal variety,it has good value for medicine and food.The aim of this study was to investigate the protective effect of Bianliang Ziyu extract(BZE)on APAP-damaged rats and the potential molecular mechanism.METHODS Male Sprague-Dawley rats(200-220 g)were intragastrically administered BZE(110,220 and 440 mg·kg^-1)for 8 d.On the ninth day,APAP(800 mg·kg^-1)was administered intragastrically to the rats 0.5 h after BZE administration to induced drug-induced liver injury.The serum and liver samples were collected after 24 h.The levels of alanine aminotransferase(ALT),aspartic aminotransferase(AST),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in serum and liver tissue of rats were detected by kit method.HE staining was used to observe the histopathological changes in the liver of rat.The effects of BZE on the expression of the oxidative stress related proteins and the mitochondrial biosyn⁃thesis related proteins were detected by Western blot.RESULTS The results showed that BZE significantly reduced the levels of ALT,AST,MDA and ROS and increased the levels of GSH and SOD caused by APAP.Moreover,BZE increased phosphorylation of AMP-activated protein kinase(AMPK)and glycogen synthase kinase 3β(GSK3β),promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2(Nrf2).BZE also upregulated the expression of mitochondrial biosynthesis related proteins such as peroxisome proliferator-activated receptorγ(PPAR-γ),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),mitochondrial transcription factor(TFAM)and nuclear respira⁃tory factor 1(NRF1).CONCLUSION BZE alleviates APAP-induced liver injury in rats by inhibiting oxidative stress via GSK3β-Nrf2 signaling and the mitochondrial biosynthesis pathway mediated by AMPK.

Iron metabolism, oxidative stress, and neonatal brain injury

The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of survivors will develop significant neurological disorders and lifelong disability.

The expression of oxidative stress genes related to myocardial ischemia reperfusion injury in patients with ST-elevation myocardial infarction

BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,P<0.05;N:9.27±4.75×10^(9)/L vs.3.89±0.81×10^(9)/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.

Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress

BACKGROUND：Liver ischemia reperfusion（IR）injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery.Pentoxifylline（PTX）and hypertonic saline solution（HTS）have been identified to have beneficial effects against IR injury.This study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR injury.METHODS： Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaCl 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaC1 plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-α, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase. RESULTS： HPTX significantly decreased TNF-α 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT,AST, IL-6, mitochondrial dysfunction and pulmonary myelo- peroxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION： This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.

Mailuoning suppresses H_2O_2-induced cortical neuronal injury and correlates with increased catalase activity and inhibited oxidative stress function

BACKGROUND：Mailuoning, a Chinese herb, has been widely used in China to treat acute ischemic stroke, and the major component exhibits anti-oxidative effects. However, the precise anti-oxidation pathway remains uncertain.OBJECTIVE：To validate the protective effects of Mailuoning on H202-induced primary cortical neuron injury in embryonic mice.DESIGN, TIME AND SETTING：Comparative observation and in v#ro experiments were performed at the Jiangsu Key Laboratory for Molecular Medicine from January 2008 to September 2009.MATERIALS：Mailuoning （Nanjing Jinling Medical Company, China）, reactive oxygen species （ROS） kit （Beyotime Biotechnology, China）, superoxide dismutase （SOD）, Cu/Zn SOD kit, malondialdehyde （MDA） kits （Nanjing Jiancheng, China）, mitochondrial membrane potential （GMS10013.1, GENMED, USA） and catalase activity assay kit （Beyotime Biotechnology, China） were utilized for the present study.METHODS：Mouse embryonic cortical neurons were isolated and cultured with culture medium containing H2O2 （80 μmol/L） and/or Mailuoning （1.25 μg/mL） for 24 hours.MAIN OUTCOME MEASURES：Neuronal viability and death were detected by methyl thiazolyl tetrazdium and flow cytometry; ROS production was determined by flow cytometry; mitochondriai membrane potential was detected using fluorescent staining; SOD activity was detected using a modified nitroblue tetrazolium method; Cu/Zn SOD and catalase activity was detected by spectrophotometry; and MDA was determined using the lipid peroxidation method.RESULTS：H2O2 increased ROS production and MDA concentration （P 〈 0.05）, and decreased mitochondrial membrane potential, SOD, Cu/Zn SOD and catalase activity （P 〈 0.05）; the number of surviving neurons （P 〈 0.05） was also reduced. Mai/uoning reversed these changes.CONCLUSION：Mailuoning protects H2O2-induced injury in cortical cells by inhibiting ROS and MDA, increasing depolarization of mitochondrial membrane, and enhancing SOD and catalase activity.

Identification of potential oxidative stress biomarkers for spinal cord injury in erythrocytes using mass spectrometry

Oxidative stress is a hallmark of secondary injury associated with spinal cord injury.Identifying stable and specific oxidative biomarkers is of important significance for studying spinal cord injury-associated secondary injury.Mature erythrocytes do not contain nuclei and mitochondria and cannot be transcribed and translated.Therefore, mature erythrocytes are highly sensitive to oxidative stress and may become a valuable biomarker.In the present study, we revealed the proteome dynamics of protein expression in erythrocytes of beagle dogs in the acute and subacute phases of spinal cord injury using mass spectrometry-based approaches.We found 26 proteins that were differentially expressed in the acute(0–3 days) and subacute(7–21 days) phases of spinal cord injury.Bioinformatics analysis revealed that these differentially expressed proteins were involved in glutathione metabolism, lipid metabolism, and pentose phosphate and other oxidative stress pathways.Western blot assays validated the differential expression of glutathione synthetase, transaldolase, and myeloperoxidase.This result was consistent with mass spectrometry results, suggesting that erythrocytes can be used as a novel sample source of biological markers of oxidative stress in spinal cord injury.Glutathione synthetase, transaldolase, and myeloperoxidase sourced from erythrocytes are potential biomarkers of oxidative stress after spinal cord injury.This study was approved by the Experimental Animal Centre of Ningxia Medical University, China(approval No.2017-073) on February 13, 2017.

Effects of Shenqi Fuzheng injection on oxidative stress after hepatic ischemia-reperfusion injury

Objective:In order to determine Shenqi Fuzheng injection’s clinical effects and explore the impact on the SOD、MDA and liver function of patients,who underwent Hepatic ischemiareperfusion injury during the surgical operation.Methods:Forty patients were collected who were treated in Oncology Surgery of Bayi Hospital from January 2019 to August 2019.These patients were divided into control group and therapy group(Shenqi Fuzheng Injection)randomly,with 20 cases in each group.In the control group,one was switched to RF treatment during operation,one was only partially blocked during operation,and the remaining 38 cases completed the study.These remained patients were all operated with Pringle maneuver,then were treated with anti-infection,liver protection,acid suppression,fluid replacement,intravenous nutrition support and other symptomatic treatment after surgery.In addition,for the patients in the therapy group,the treatment of Shenqi Fuzheng injection were added once a day,which lasted 5 days.During the perioperative period,we would record their general conditions,SOD and MDA levels;liver function(ALT、AST、LDH).These data were analyzed statistically by SPSS 21.0 statistical software.Results:There was no statistically significant difference in general indicators related to the perioperative period between the two groups of patients(P>0.05).There was no significant difference in SOD and MDA levels between the two groups(P>0.05).,but at 1d,3d,and 5d after operation,the SOD level in the observation group was significantly higher than that in the control group(both P<0.05)and The MDA level in the observation group was significantly lower than the control group.The differences were statistically significant(all P<0.05).There was no significant difference in ALT and AST levels between the two groups before and after surgery(P>0.05),while the LDH levels in the two groups were not statistically different before surgery,on the first day after surgery,and on the third day after surgery(P>0.05),while there were statistical differences on the fifth day after surgery(P<0.05).Conclusions:For the pathients who received hepatectomy with Pringle maneuver,using Shenqi Fuzheng injection could improve the activity of antioxidant enzymes in the body,reduce the production of lipid peroxides,inhibit the oxidative stress response in the process of HIRI,thus it played a role in protecting the liver and accelerated the recovery.

Advances in oxidative stress and NOD-like/toll-like receptors in acute renal injury

Acute Kidney Injury(AKI)is a clinical syndrome characterized by rapid renal deterioration with high morbidity and mortality.Renal reperfusion(IRI),renal toxicity and sepsis are the main causes of AKI.IRI is one of the main causes of acute kidney injury in clinic,accounting for 75%of all the causes of AKI[1].The fatality rate of AKI caused by IRI is high,and the surviving patients may leave chronic renal impairment with different degrees[2].A number of studies have shown that ischemia-reperfusion injury leading to renal dysfunction is directly related to oxidative stress,and the inhibition of oxidative stress through nod-like/toll-like signaling pathway can reduce acute renal injury.This review summarizes the research progress in regulating oxidative stress and the relationship between innate immune receptors and acute renal injury.

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

Acute myocardial infarction(AMI) is the leading cause of death worldwide. Its associated mortality, morbidity and complications have significantly decreased with the development of interventional cardiology and percutaneous coronary angioplasty(PCA) treatment, which quick-ly and effectively restore the blood flow to the area previously subjected to ischemia. Paradoxi-cally, the restoration of blood flow to the ischemic zone leads to a massive production of reactive oxygen species(ROS) which generate rapid and severe damage to biomolecules, generating a phenomenon called myocardial reperfusion injury(MRI). In the clinical setting, MRI is associated with multiple complications such as lethal reperfusion, no-reflow, myocardial stunning, and reperfusion arrhythmias. Despite significant advances in the understanding of the mechanisms accounting for the myocardial ischemia reperfusion injury, it remains an unsolved problem. Although promising results have been obtained in experimental studies(mainly in animal models), these benefits have not been translated into clinical settings. Thus, clinical trials have failed to find benefits from any therapy to prevent MRI. There is major evidence with respect to the contribution of oxidative stress to MRI in cardiovascular diseases. The lack- of consistency between basic studies and clinical trials is not solely based on the diversity inherent in epidemiology but is also a result of the methodological weak-nesses of some studies. It is quite possible that pharmacological issues, such as doses, active ingredients, bioavailability, routes of administration, co-therapies, startup time of the drug intervention,and its continuity may also have some responsibility for the lack- of consistency between different studies. Furthermore, the administration of high ascorbate doses prior to reperfusion appears to be a safe and rational therapy against the development of oxidative damage associated with myocardial reperfusion. In addition, the association with N-acetylcysteine(a glutathione donor) and deferoxamine(an iron chelator) could improve the antioxidant cardioprotection by ascorbate, mak-ing it even more effective in preventing myocardial reperfusion damage associated with PCA following AMI.

GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats

Hydrogen sulfide （H2S） is a gasotransmitter that regulates cardiovascular functions. The present study aimed to determine the protective effect of slow-releasing H2S donor GYY4137 on myocardial ischemia and reperfusion （I/R） injury and to investigate the possible signaling mechanisms involved. Male Sprague-Dawley rats were treated with GYY4137 at 12.5 mg/（kg.day）, 25 mg/（kg.day） or 50 mg/（kg.day） intraperitoneally for 7 days. Then, rats were subjected to 30 minutes of left anterior descending coronary artery occlusion followed by reperfusion for 24 hours. We found that GYY4137 increased the cardiac ejection fraction and fractional shortening, reduced the ischemia area, alleviated histological injury and decreased plasma creatine kinase after myocardial I/R. Both H2S concentration in plasma and cystathionine-γ-lyase （CSE） activity in the myocardium were enhanced in the GYY4137 treated groups. GYY4137 also decreased malondialdehyde and myeloperoxidase levels in serum, attenuated superoxide anion level and suppressed phosphorylation of mitogen activated protein kinases in the myocardium after I/R. Meanwhile, GYY4137 increased the expression of Bcl-2 but decreased the expression of Bax, caspase-3 activity and apoptosis in the myocardium. The data suggest that GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis.

Sphingosine kinase 1 knockout alleviates hepatic ischemia/reperfusion injury by attenuating inflammation and oxidative stress in mice

Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in multiple bioactive processes. However, little is known about the role of Sph K1 in hepatic I/R injury. This study aimed to investigate the effect of Sph K1 knockout on liver I/R injury and to explore underlying mechanisms. Methods: Sph K1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3(STAT3). Western blotting was used to determine the expression of S1 P receptor 1(S1 PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. Results: Sph K1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in Sph K1 knockout mice as demonstrated by attenuated expression of S1 PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1 β, interleukin-6 and tumor necrosis factor-α were also inhibited by Sph K1 genetic deletion. The oxidative stress markers were lower in Sph K1 knockout mice after I/R injury than wild type mice. Conclusions: Knockout of Sph K1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. Sph K1 may be a novel and potent target in clinical practice in I/R-related liver injury.