Protective effects of polyethylene oxide on the vascular and organ function of rats with severe hemorrhagic shock

This study examined the effects of polyethylene oxide (PEO) on the survival rate, hemodynamics, blood gas indexes, lactic acid levels, microcirculation, and inflammatory cytokine levels in rats subjected to severe hemorrhagic shock. The shocked rats were resuscitated with either Ringer’s lactate solution or 20 ppm of PEO in Ringer’s lactate solution for 1 h. It was found that infusion of PEO effectively improved the survival, metabolic acidosis, oxygen delivery, hyperlactacidemia, tissue perfusion, and inflammatory responses of rats subjected to hemorrhagic shock. In addition, we found, for the first time, that PEO showed protective effects on hepatic and renal injury, as evidenced by the significant decreases in the elevated levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine caused by shock induction after infusion of PEO (p < 0.05, 60 min post-resuscitation by comparison with pre-resuscitation). All of these findings indicate that PEO exhibits strong therapeutic effects under conditions of severe hemorrhagic shock,which also provides theoretical and experimental bases for the clinical use of PEO.

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Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

Scientific Reports ◽

10.1038/s41598-020-79607-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shinjini Chakraborty ◽

Veronika Eva Winkelmann ◽

Sonja Braumüller ◽

Annette Palmer ◽

Anke Schultze ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Inflammatory Responses ◽

Experimental Models ◽

Lung Damage ◽

C5a Receptor ◽

Cytokine Levels ◽

Vitro Model

AbstractSingular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS. The aim of the study was to assess early modulation of inflammatory responses and lung damage 4 h after PT + HS induction. NoxD21-treated PT + HS mice displayed greater polymorphonuclear cell recruitment in the lung, increased pro-inflammatory cytokine levels in the bronchoalveolar lavage fluids (BALF) and reduced myeloperoxidase levels within the lung tissue. An in vitro model of the alveolar-capillary barrier was established to confirm these in vivo observations. Treatment with a polytrauma cocktail induced barrier damage only after 16 h, and NoxD21 treatment in vitro did not rescue this effect. Furthermore, to test the exact role of both the cognate receptors of C5a (C5aR1 and C5aR2), experimental PT + HS was induced in C5aR1 knockout (C5aR1 KO) and C5aR2 KO mice. Following 4 h of PT + HS, C5aR2 KO mice had significantly reduced IL-6 and IL-17 levels in the BALF without significant lung damage, and both, C5aR1 KO and C5aR2 KO PT + HS animals displayed reduced MPO levels within the lungs. In conclusion, the C5aR2 could be a putative driver of early local inflammatory responses in the lung after PT + HS.

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Orientin Ameliorates LPS-Induced Inflammatory Responses through the Inhibitory of the NF-κB Pathway and NLRP3 Inflammasome

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/2495496 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Qingfei Xiao ◽

Zhihui Qu ◽

Ying Zhao ◽

Liming Yang ◽

Pujun Gao

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammatory Responses ◽

Receptor Protein ◽

Raw 264.7 Cells ◽

Prostaglandin E ◽

Inflammasome Activation ◽

Therapeutic Effects ◽

Protective Effects ◽

Nlrp3 Inflammasome Activation ◽

Underlying Mechanisms

Inflammation is a complex response to diverse pathological conditions, resulting in negative rather than protective effects when uncontrolled. Orientin (Ori), a flavonoid component isolated from natural plants, possesses abundant properties. Thus, we aimed to discover the potential therapeutic effects of orientin on lipopolysaccharide- (LPS-) induced inflammation in RAW 264.7 cells and the underlying mechanisms. In our studies, we evaluated the effects of Ori on proinflammatory mediator production stimulated by LPS, including tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-18, and IL-1β, along with prostaglandin E2 (PGE2) and NO. Our data indicated that orientin dramatically inhibited the levels of these mediators. Consistent with these results, the expression levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also reduced. Further study demonstrated that such inhibitory effects of Ori were due to suppression of the nuclear factor-kappa B (NF-κB) pathway and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) inflammasome activation, which may contribute to its anti-inflammatory effects. Together, these findings show that Ori may be an effective candidate for ameliorating LPS-induced inflammatory responses.

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The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8026838 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

Zhao Gao ◽

Jiecheng Zhang ◽

Li Wei ◽

Xingping Yang ◽

Yuan Zhang ◽

...

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Farnesoid X Receptor ◽

Sirtuin 1 ◽

Therapeutic Effects ◽

Dependent Manner ◽

Protective Effects ◽

Hepatocyte Apoptosis ◽

Apap Overdose ◽

First Time

Acetaminophen (APAP) toxicity leads to severe acute liver injury (ALI) by inducing excessive oxidative stress, inflammatory response, and hepatocyte apoptosis. Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose.

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Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF-κB Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/1791789 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Lie-Qiang Xu ◽

Xiu-Ting Yu ◽

Shu-Hua Gui ◽

Jian-hui Xie ◽

Xiu-Fen Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Therapeutic Agent ◽

Inflammatory Responses ◽

Intratracheal Instillation ◽

Inflammatory Cells ◽

Therapeutic Effects ◽

Protective Effects ◽

Lung Histopathology

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responsesviadecreasing the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPSviainhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting.

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MODERATE RINGER'S LACTATE SOLUTION RESUSCITATION YIELDS BEST NEUROLOGICAL OUTCOME IN CONTROLLED HEMORRHAGIC SHOCK COMBINED WITH BRAIN INJURY IN RATS

Shock ◽

10.1097/shk.0b013e3181ce2cbc ◽

2010 ◽

Vol 34 (1) ◽

pp. 75-82 ◽

Cited By ~ 11

Author(s):

Dalit E. Dar ◽

Jean F. Soustiel ◽

Menashe Zaaroor ◽

Evgeni M. Brotfain ◽

Akiva Leibowitz ◽

...

Keyword(s):

Brain Injury ◽

Hemorrhagic Shock ◽

Neurological Outcome ◽

Ringer’S Lactate ◽

Lactate Solution

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PPARγ in Ischemia-Reperfusion Injury: Overview of the Biology and Therapy

Frontiers in Pharmacology ◽

10.3389/fphar.2021.600618 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ruizhen Huang ◽

Chiyu Zhang ◽

Xing Wang ◽

Honglin Hu

Keyword(s):

Reperfusion Injury ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Tissue Perfusion ◽

Traumatic Shock ◽

Peroxisome Proliferator ◽

Protective Effects ◽

Peroxisome Proliferator Activated Receptor ◽

Promising Therapeutic Target

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that is often characterized as a blood circulation disorder caused due to various factors (such as traumatic shock, surgery, organ transplantation, burn, and thrombus). Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. Theoretically, IRI can occur in various tissues and organs, including the kidney, liver, myocardium, and brain, among others. The advances made in research regarding restoring tissue perfusion in ischemic areas have been inadequate with regard to decreasing the mortality and infarct size associated with IRI. Hence, the clinical treatment of patients with severe IRI remains a thorny issue. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of a superfamily of nuclear transcription factors activated by agonists and is a promising therapeutic target for ameliorating IRI. Therefore, this review focuses on the role of PPARγ in IRI. The protective effects of PPARγ, such as attenuating oxidative stress, inhibiting inflammatory responses, and antagonizing apoptosis, are described, envisaging certain therapeutic perspectives.

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Rhoifolin Ameliorates Osteoarthritis via Regulating Autophagy

Frontiers in Pharmacology ◽

10.3389/fphar.2021.661072 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiyuan Yan ◽

Bowei Ni ◽

Gaohong Sheng ◽

Yingchi Zhang ◽

Yifan Xiao ◽

...

Keyword(s):

Inflammatory Responses ◽

Cartilage Damage ◽

Cartilage Degradation ◽

Joint Disease ◽

Signal Pathways ◽

Therapeutic Effects ◽

Protective Effects ◽

Age Related ◽

Anti Inflammatory

Osteoarthritis (OA) is a common age-related joint disease. Its development has been generally thought to be associated with inflammation and autophagy. Rhoifolin (ROF), a flavanone extracted from Rhus succedanea, has exhibited prominent anti-oxidative and anti-inflammatory properties in several diseases. However the exact role of ROF in OA remains unclear. Here, we investigated the therapeutic effects as well as the underlying mechanism of ROF on rat OA. Our results indicated that ROF could significantly alleviate the IL-1β–induced inflammatory responses, cartilage degradation, and autophagy downregulation in rat chondrocytes. Moreover, administration of autophagy inhibitor 3-methyladenine (3-MA) could reverse the anti-inflammatory and anti-cartilage degradation effects of ROF. Furthermore, P38/JNK and PI3K/AKT/mTOR signal pathways were involved in the protective effects of ROF. In vivo, intra-articular injection of ROF could notably ameliorate the cartilage damage in rat OA model. In conclusion, our work elucidated that ROF ameliorated rat OA via regulating autophagy, indicating the potential role of ROF in OA therapy.

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A Murine Model Of Hemorrhagic Shock/Resuscitation Demonstrates Transfusion Related Acute Lung Injury (TRALI) Induced By Stored Platelet Transfusions

Blood ◽

10.1182/blood.v122.21.789.789 ◽

2013 ◽

Vol 122 (21) ◽

pp. 789-789

Author(s):

Christopher G.J. McKenzie ◽

Michael Kim ◽

Dana Safavian ◽

Ori D Rotstein ◽

John W. Semple

Keyword(s):

Acute Lung Injury ◽

Animal Models ◽

Lung Injury ◽

Hemorrhagic Shock ◽

Conflicts Of Interest ◽

Hypovolemic Shock ◽

Second Hit ◽

Ringer’S Lactate ◽

Lactate Solution

Abstract Transfusion related acute lung injury (TRALI) is one of the leading causes of transfusion fatalities. There have been several animal models of TRALI developed including ex vivo lung models demonstrating the importance of human anti-neutrophil antibodies in TRALI and in vivo transfusion models showing how biological response modifiers can induce recipient lung damage. In addition, an in vivo antibody-mediated TRALI model has also been established and has shown close similarities with human TRALI. Most of the animal models have a two-hit paradigm where the first hit is delivered in the form of a noxious substance such as lipopolysaccharide and the second hit is a transfusion of either a blood product or an antibody. Here we describe a novel clinically relevant two-hit model where the first hit is hemorrhagic shock followed by a second hit in the form of a platelet transfusion. Severe combined immunodeficient (SCID) mice were anesthetized and had half of their total blood volume was removed via a carotid cannula to instigate hypovolemic shock. After one hour of shock, the mice were reperfused with either Ringer’s lactate solution or fresh or three day aged platelets. 34-1-2s, a monoclonal anti-mouse MHC class I antibody known to induce TRALI was used as a positive reperfusion control. Two hours following reperfusion, the mice were sacrificed and blood was obtained via cardiac puncture in order to measure serum levels of the neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2). Lungs were removed to determine the percentage of accumulated neutrophils and to measure edema. Compared with control mice reperfused with Ringer’s lactate solution or mice administered fresh platelets, serum MIP-2 levels in mice administered with three day aged platelets were significantly elevated and were comparable to those observed in mice infused with 34-1-2s. Pulmonary neutrophil accumulation in the mice transfused with 3 day stored platelets was also elevated to levels observed in 34-1-2s treated mice. Pulmonary edema as measured by lung Wet/Dry ratios was elevated in mice receiving the 3 day aged platelets. In vivo administration of a MIP-2 antagonist (SB225002, 4mg/kg) intraperitoneally immediately before reperfusion significantly reduced all TRALI symptoms. These results show that an animal model of hypovolemic shock exhibits TRALI upon reperfusion with stored platelets and is dependent on MIP-2 production. This clinically-relevant model will be valuable in studying potential therapeutic interventions to prevent TRALI following transfusions, Disclosures: No relevant conflicts of interest to declare.

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Protective effects of curcumin against lipopolysaccharide-induced toxicity

Current Medicinal Chemistry ◽

10.2174/0929867328666210525124707 ◽

2021 ◽

Vol 28 ◽

Author(s):

Ali Ganji ◽

Iman Farahani ◽

Amir Mohammad Saeedifar ◽

Ghasem Mosayebi ◽

Ali Ghazavi ◽

...

Keyword(s):

Septic Shock ◽

Inflammatory Responses ◽

Experimental Investigations ◽

Inflammasome Activation ◽

Therapeutic Effects ◽

Protective Effects ◽

Therapeutic Approaches ◽

Cell Wall Component ◽

Gram Negative ◽

Surface Receptors

Background: Lipopolysaccharide (LPS), a Gram-negative bacterial cell wall component, evokes intensive inflammatory responses in the human body. Naturally, inflammation is a part of the host immune response to an infection; nonetheless, an exaggerated response can lead to a series of pathophysiological consequences, collectively known as LPS toxicity or septic shock. Objective: This review will explore the cellular and experimental investigations that mainly focus on Curcumin's therapeutic effects on the LPS-mediated inflammatory responses. Method: A literature review of all relevant studies was performed. Conclusion : Curcumin has been reported to exert anti-inflammatory properties by interfering with LPS-induced inflammatory pathways, including binding to cell surface receptors of LPS, NF-kB activation pathway, and inflammasome activation. Further clinical studies on the effect of Curcumin in reducing the pathophysiological consequences of LPS toxicity would substantiate the use of this molecule for future therapeutic approaches.

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Astilbin fromSmilax glabraRoxb. Attenuates Inflammatory Responses in Complete Freund’s Adjuvant-Induced Arthritis Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8246420 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Lisha Dong ◽

Jinqiu Zhu ◽

Hongzhi Du ◽

Heng Nong ◽

Xicheng He ◽

...

Keyword(s):

Inflammatory Response ◽

Inflammatory Responses ◽

Joint Damage ◽

Guizhou Province ◽

Red Cross ◽

Flavonoid Compound ◽

Therapeutic Effects ◽

Inhibitory Effects ◽

Protein Activity ◽

Cytokine Levels

Astilbin, a flavonoid compound, was isolated from the rhizome ofSmilax glabraRoxb. (with red cross-section) grown in Guizhou Province, China. We accessed its effect and potential mechanism on attenuation of the inflammatory response in CFA-induced AA rats. Our results showed that daily oral administration of astilbin at 5.3 mg/kg reduced joint damage in the hind paw of AA rats. Accordingly, astilbin exhibited remarkable inhibitory effects on TNF-α, IL-1β, and IL-6 mRNA expression. Significant decrease of serum cytokine levels of TNF-α, IL-1β, and IL-6 was also observed in astilbin-treated AA rats compared to the vehicle-treated AA rats. The reduced expression of these cytokines was associated with protein activity suppression of three key molecular targets in the pathogenesis of RA, including IKKβ, NF-κB p65 subunit, and TLR adaptor MyD88. Furthermore, the therapeutic effects of astilbin on the inhibition of cytokines production as well as the reduction of inflammatory response in AA rats are close to a commonly used antirheumatic drug, leflunomide. Collectively, our data suggest that the action mechanism of astilbin, as an anti-inflammatory agent for RA treatment, is associated with modulating the production of proinflammatory cytokines and inhibiting the expression of key elements in NF-κB signaling pathway mediated by TLR.

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