Assessment of Sumatriptan on Sepsis-Induced Kidney injury in the Cecal Ligation and Puncture Mice Model

Drug Research ◽  
2021 ◽  
Author(s):  
Hasan Yousefi-Manesh ◽  
Samira Shirooie ◽  
Tayebeh Noori ◽  
Seyed Mohammad Tavangar ◽  
Mohammad Sheibani ◽  
...  
Keyword(s):  
Immune Response ◽  
Mortality Rate ◽  
Inflammatory Cytokines ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Protective Effects ◽  
Cecal Ligation And Puncture ◽  
Term Survival ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractSepsis is a severe systemic inflammatory response with high mortality rate resulting from different microorganisms. Cytokines activation is essential for the immune response, but in painful conditions like sepsis, cytokines act as a double-edged sword and dysregulate immune response which is life-threatening owing to multiple organ dysfunction. The abnormality in 5-HT function is involved in pathological conditions like irritable bowel syndrome, inflammation, myocardial ischemia, itch and renal injury. Sumatriptan, a 5-HT1B/1D agonist, has anti-inflammatory and anti-oxidative stress effects on animal models. This study was aimed to assess the effects of sumatriptan on kidney injury, the levels of pro-inflammatory cytokines and the percentage of survival in (CLP)-induced sepsis were examined.Cecal ligation and puncture (CLP) model was done on adult C57BL/6 male mice to induce Polymicrobial sepsis. Sumatriptan was injected intraperitoneally 1 h after the sepsis induction by CLP at doses of 0.1, 0.3, and 1 mg/kg in 3 treatment groups. To study the effect of sumatriptan on short-term survival, septic animals were detected 72 h after CLP. Serum levels of TNF-α, IL-1β, IL-6 and IL-10 were evaluated. To study sepsis-induced acute renal failure, kidney functional biomarkers and histopathological alterations were evaluated.Sumatriptan (0.3 mg/kg) administration significantly enhanced survival rate (P<0.01) compared to the CLP group. The beneficial effects of sumatriptan were related to a significant decrease in the pro-inflammatory cytokines and elevated level of IL-10. Sumatriptan presented protective effects on kidney biomarkers and histopathology assay.Anti-inflammatory effects of sumatriptan lead to decrease mortality rate and inflammatory cytokines in CLP induction sepsis in C57BL/6 mice.

Glatiramer acetate treatment inhibits inflammatory responses and improves survival in a mice model of cecal ligation and puncture-induced sepsis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elahe Maleki ◽  
Mohammad Sheibani ◽  
Sadaf Nezamoleslami ◽  
Ahmad Reza Dehpour ◽  
Nasrin Takzaree ◽  
...  
Keyword(s):  
Survival Rate ◽  
Glatiramer Acetate ◽  
Inflammatory Cytokines ◽  
Cecal Ligation ◽  
Protective Effects ◽  
Cecal Ligation And Puncture ◽  
Mice Model ◽  
Term Survival ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Objectives Sepsis is a clinical crisis which has been considered as one of the important causes of mortality across the world. We hypothesized that modulation of hyper-inflammatory phase of sepsis pathophysiology can lead to protective effects on survival outcome. Glatiramer acetate (GA) is a neuroprotective drug commonly used in multiple sclerosis (MS). GA is characterized by immunom activity via regulation of innate and adaptive immunity. This study was designed to evaluate the acute treatment with GA on initial inflammatory response-induced mortality in septic mice. Methods Cecal ligation and puncture (CLP) model was operated on male mice as a model of Polymicrobial sepsis. GA was administrated intraperitoneally after the sepsis induction at doses of 0.5, 1, and 2 mg/kg in three treatment groups. To investigate the effect of GA on short-term survival, septic mice were observed during 72 h after CLP. Serum levels of TNF-α, IL-1β, and IL-6 as pro-inflammatory cytokines and also IL-10 as a critical anti-inflammatory cytokine were analysed. To consider sepsis-induced acute kidney injury, renal functional biomarkers and histopathological changes was assessed. Results GA treatment significantly improved survival rate at doses of 1, and 2 mg/kg. Survival improvement was accompanied by remarkable reduction in the pro-inflammatory cytokines and enhanced production of IL-10. GA showed to have protective effects on renal function as well. Conclusions Immunomodulatory and anti-inflammatory properties of GA resulted in increase in survival rate and decrease in inflammatory markers in mice model of cecal ligation and puncture–induced sepsis.

Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in the microglia.

2020 ◽  
Author(s):  
Shao-Peng Lin ◽  
Jue-Xian Wei ◽  
Shan Ye ◽  
Jiasong Hu ◽  
Jingyi Bu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Neuronal Damage ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Neurocognitive Deficits ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in neurocognitive deficits associated with sepsis remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of artemisinin on cognitive impairment resulting from sepsis.Methods: Male C57BL/6 mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of sepsis. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical and ELISA analysis. Additionally, the protective mechanism of artemisinin was determined in vitro.Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. The in vitro experiment revealed that artemisinin could reduce the production of pro-inflammatory cytokines and suppress the microglial migration in the BV2 microglia cells. Meanwhile, western blot demonstrated that artemisinin suppressed nuclear translocation of nuclear factor kappa-B and the expression of pro-inflammatory cytokines (i.e. tumor necrosis factor alpha, interleukin-6) by activating adenosine monophosphate-activated protein kinaseα1 (AMPKα1) pathway. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin.Conclusion: Artemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect was probably mediated by the activation of AMPKα1 signalling pathway in microglia.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P&lt;0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

2020 ◽  
Author(s):  
Bruna Lima Correa ◽  
Nadia El Harane ◽  
Ingrid Gomez ◽  
Hocine Rachid Hocine ◽  
José Vilar ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Nk Cell ◽  
Inflammatory Monocytes ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Aims The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Methods and results Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages. Conclusions EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.

scholarly journals Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jeonghyeon Moon ◽  
Seon-yeong Lee ◽  
Jeong Won Choi ◽  
A Ram Lee ◽  
Jin Hee Yoo ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Th17 Cells ◽  
Skin Fibroblasts ◽  
Inflammatory Factors ◽  
Metformin Treatment ◽  
Protective Effects ◽  
Stat3 Signaling ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractScleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α play important roles in the pathogenesis of scleroderma. Because metformin, a medication used to treat diabetes, has effective immunoregulatory functions, we investigated its therapeutic function in scleroderma. Mice in a model of bleomycin-induced scleroderma were treated with metformin for 2 weeks. Histological assessment demonstrated protective effects of metformin against scleroderma. Metformin decreased the expression of pro-inflammatory factors in dermal tissue and lymphocytes. It also decreased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) and fibrosis-inducing molecules both in vivo and in vitro. These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1β, IL-6, and TNF-α. To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment. These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.

scholarly journals Celecoxib Decrease Seizures Susceptibility in a Rat Model of Inflammation by Inhibiting HMGB1 Translocation

2021 ◽  
Vol 14 (4) ◽  
pp. 380
Author(s):  
Hadeel Alsaegh ◽  
Hala Eweis ◽  
Fatemah Kamal ◽  
Aziza Alrafiah
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Control Group ◽  
Protective Effects ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Inflammatory Models ◽  
Anti Inflammatory ◽  
Lung And Kidney ◽  
Pro Inflammatory Cytokines

The risk of developing epilepsy is strongly linked to peripheral inflammatory disorders in humans. High-mobility group box protein 1 (HMGB1) has the most focus for being a suspect in this scenario. The current study aimed to detect the celecoxib effect, an anti-inflammatory drug, on decreasing seizure susceptibility and organ damage in lipopolysaccharides (LPS)/pilocarpine (PILO) pretreated Wistar rats. Rats were divided into 6 groups (8 each): group 1 (control), group 2 (PILO), group 3 (PILO+LPS), group 4 (PILO+LPS+(VPA) Valproic acid), group 5 (PILO+LPS+Celecoxib), and group 6 (PILO+LPS+VPA+Celecoxib). LPS was used to induce sepsis and PILO to induce seizures. Oxidative stress markers, pro-inflammatory cytokines, and HMGB1 levels in serum and brain homogenate were evaluated. Histopathological studies were conducted on the hippocampus, liver, lung, and kidney. Treatment with celecoxib either alone or in combination with VPA significantly reduced Racine score and delays latency to generalized tonic-clonic seizures onset with a significant decrease in hippocampal levels of pro-inflammatory cytokines, oxidative stress markers, and increase in reduced glutathione. In addition, celecoxib treatment either alone or in combination with VPA suppressed HMGB1translocation into peripheral circulation more than treatment with VPA alone. Furthermore, hippocampus, liver, lung, and kidney histopathological changes were improved in contrast to other epileptic groups. Celecoxib either alone or combined with VPA has antiepileptic and multiorgan protective effects on acute seizures and inflammatory models induced by PILO with LPS. It decreased histopathological findings, oxidative, and inflammatory effects induced by VPA and LPS. This might be due to its anti-oxidative, anti-inflammatory and anti-HMGB1 mediated effects.

scholarly journals Adenine Nucleotide Translocase 1 Expression Modulates the Immune Response in Ischemic Hearts

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2130
Author(s):  
Fatih Yergöz ◽  
Julian Friebel ◽  
Nicolle Kränkel ◽  
Ursula Rauch-Kroehnert ◽  
Heinz-Peter Schultheiss ◽  
...  
Keyword(s):  
Immune Response ◽  
Growth Factor ◽  
Inflammatory Cytokines ◽  
Adenine Nucleotide ◽  
Left Ventricular ◽  
Macrophage Infiltration ◽  
Adenine Nucleotide Translocase ◽  
Inflammatory Immune Response ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Adenine nucleotide translocase 1 (ANT1) transfers ATP and ADP over the mitochondrial inner membrane and thus supplies the cell with energy. This study analyzed the role of ANT1 in the immune response of ischemic heart tissue. Ischemic ANT1 overexpressing hearts experienced a shift toward an anti-inflammatory immune response. The shift was characterized by low interleukin (IL)-1β expression and M1 macrophage infiltration, whereas M2 macrophage infiltration and levels of IL-10, IL-4, and transforming growth factor (TGFβ) were increased. The modulated immune response correlated with high mitochondrial integrity, reduced oxidative stress, low left ventricular end-diastolic heart pressure, and a high survival rate. Isolated ANT1-transgenic (ANT1-TG) cardiomyocytes expressed low levels of pro-inflammatory cytokines such as IL-1α, tumor necrosis factor α, and TGFβ. However, they showed increased expression and cellular release of anti-inflammatory immunomodulators such as vascular endothelial growth factor. The secretome from ANT1-TG cardiomyocytes initiated stress resistance when applied to ischemic wild-type cardiomyocytes and endothelial cells. It additionally prevented macrophages from expressing pro-inflammatory cytokines. Additionally, ANT1 expression correlated with genes that are related to cytokine and growth factor pathways in hearts of patients with ischemic cardiomyopathy. In conclusion, ANT1-TG cardiomyocytes secrete soluble factors that influence ischemic cardiac cells and initiate an anti-inflammatory immune response in ischemic hearts.

scholarly journals Tripterygium glycoside improves regulatory T cells and attenuates acute organ dysfunction in septic mice

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Xiaoming Zhang ◽  
Xiaojie Zhou
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cecal Ligation ◽  
Multiple Organ ◽  
Protective Effects ◽  
Cecal Ligation And Puncture ◽  
Mice Model ◽  
Tnf Α ◽  
Lung And Kidney ◽  
Pro Inflammatory Cytokines

Sepsis is a fatal infectious disease accompanied by multiple organ failure. Immune dysfunction and inflammatory response play an important role in the progression of the disease. Tripterygium glycoside (TG) has immune suppression and anti-inflammatory effects. Here, we investigated the effects of TG on cecal ligation and puncture (CLP)-induced sepsis. Septic mice model was induced by cecal ligation and puncture(CLP), after administration of TG, specimens are collected at designated time points. Histopathology changes of lung tissues and Kidney tissues were observed under light microscope, magnetic microbeads were used to isolate splenic CD4+CD25+ regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. ELISA method was employed to detect the concentrations of plasma TNF-α, IL-6, and IL-10. Nuclear p-NF-κB and Cytoplasmic IkB-a was detected by western blot. TG administration significantly alleviated lung and kidney inflammatory injury and improved the survival of septic mice. Furthermore, the suppressive function of regulatory T cells was enhanced and plasma expression of IL-10 was increased following TG treatment. The NF-B signaling pathway and secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with TG. TG exerts protective effects through improving regulatory T cells and attenuating pro-inflammatory cytokines in septic mice.

scholarly journals Impact of Pycnogenol on Acetaminophen-Induced Hepatorenal Damage

2021 ◽  
Vol 12 (6) ◽  
pp. 8070-8080
Keyword(s):  
Inflammatory Cytokines ◽  
Kidney Tissue ◽  
Albino Rats ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Tissue Samples ◽  
Liver And Kidney ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

We investigated the protective effects of pycnogenol (PYC), a natural anti-oxidant with an anti-inflammatory effect, on the acetaminophen (APAP)-induced hepatorenal injury in rats. Wistar albino rats were divided into four experimental groups: control, PYC (10 mg/kg, ip), APAP (1000 mg/kg), and APAP+PYC groups. Rats were decapitated 24 hours after the APAP injection, and their blood was taken to determine blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines; TNF-α and IL-1 β. Liver and kidney tissue samples were obtained for the histological examination and the determination of malondialdehyde (MDA) and glutathione (GSH) levels as well as myeloperoxidase (MPO) and Na+/K+-ATPase activities. PYC treatment decreased the APAP-induced elevations in serum pro-inflammatory cytokines and reduced the impairment of liver and kidney functions. Furthermore, the increase in tissue lipid peroxidation and myeloperoxidase activity and the decrease in the GSH levels and Na+/K+-ATPase activity by the APAP overdose were reversed by the PYC treatment. Besides, histologic findings reinforce the protective effect of PYC in APAP-induced hepatorenal damage. PYC, which appears to have restored the GSH and depressed neutrophil infiltration and the associated release of pro-inflammatory cytokines, merits consideration as an anti-oxidant and anti-inflammatory agent in preventing APAP-induced hepatorenal damage.

Metformin Ameliorates Scleroderma Via Inhibiting Th17 Cells and Reducing mTOR-STAT3 Signaling in Skin Fibroblasts

2021 ◽  
Author(s):  
Jeonghyeon Moon ◽  
Seon-yeong Lee ◽  
Jeong Won Choi ◽  
Aram Lee ◽  
Jin Hee Yoo ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Th17 Cells ◽  
Skin Fibroblasts ◽  
Inflammatory Factors ◽  
Metformin Treatment ◽  
Protective Effects ◽  
Stat3 Signaling ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Scleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α play important roles in the pathogenesis of scleroderma. Because metformin, a medication used to treat diabetes, has effective immunoregulatory functions, we investigated its therapeutic function in scleroderma. Mice in a model of bleomycin-induced scleroderma were treated with metformin for 2 weeks. Histological assessment demonstrated protective effects of metformin against scleroderma. Metformin decreased the expression of pro-inflammatory factors in dermal tissue and lymphocytes. It also decreased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) and fibrosis-inducing molecules both in vivo and in vitro. These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1β, IL-6, and TNF-α. To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that mTOR and STAT3 protein expression were decreased by metformin treatment. These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.

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