scholarly journals Anti-inflammatory and protective effects of combined treatment with sitagliptin and melatonin in cardiac ischemia reperfusion injury in obese rats: Involvement of TLR-4/NF-κB pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110662
Author(s):  
Hailei Sun ◽  
Zhengchun Zhou ◽  
Haiyang Xuan ◽  
Zhongya Yan
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Myocardial Infarct Size ◽  
High Fat ◽  
Early Reperfusion ◽  
Obese Rats ◽  
Cox 2 ◽  
Pro Inflammatory Cytokines

Background: Obesity is associated with an augmented risk of myocardial ischemia/reperfusion (I/R) injury. Reduction of I/R injury by effective cardioprotective strategies needs to be investigated in obese subjects. This study aimed to evaluate the combined effects of sitagliptin and melatonin on inflammatory response and TLR4/IκBα/NF-κB signaling following cardiac I/R damage in obese rats. Methods: Sixty-six male Wistar rats (180–200 g) were fed a low fat diet (10% Kcal from lipids) or high fat (45% Kcal from lipids) diets for 12 weeks. High fat-fed (obese) rats experienced 30 min left anterior descending occlusion followed by 24 h reperfusion. Obese rats received sitagliptin (20 mg/kg/day) for 1 month before I/R surgery. Melatonin (10 mg/kg) was injected at early reperfusion. Myocardial infarct size (IS), cTn-I release, pro-inflammatory cytokines, myeloperoxidase (MPO), COX-2 and iNOS, and the protein expressions of TLR4, p-NF-κB/p65, and p-IκBα were evaluated. Results: Monotherapies with sitagliptin-preconditioning or melatonin-postconditioning had no cardioprotective effects in obese rats. However, combined therapy with sitagliptin and melatonin significantly reduced IS, and the release of cTn-I, in comparison to untreated obese rats ( p < .01) Moreover, this combination decreased the production of pro-inflammatory cytokines, MPO, COX-2 and iNOS, and the expression of TLR4 and p-NF-κB/p65, while reduced the expression of p-IκBα, in comparison with untreated or monotherapies-received obese rats ( p < .01 for all). Conclusion: Combination therapy with sitagliptin and melatonin was a good cardioprotective strategy to modulate the inflammatory responses and TLR4/NF-κB signaling pathway in obese patients with cardiac I/R injury.

scholarly journals Dietary Betaine Mitigates Hepatic Steatosis and Inflammation Induced by a High-Fat-Diet by Modulating the Sirt1/Srebp-1/Pparɑ Pathway in Juvenile Black Seabream (Acanthopagrus schlegelii)

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Jin ◽  
Yuedong Shen ◽  
Tingting Pan ◽  
Tingting Zhu ◽  
Xuejiao Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Protein Content ◽  
Hepatic Steatosis ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
High Fat ◽  
Expression Levels ◽  
Black Seabream ◽  
Pro Inflammatory Cytokines

The present study aimed to elucidate the mechanism of dietary betaine, as a lipid-lowering substance, on the regulation of lipid metabolism and inflammation in juvenile black seabream (Acanthopagrus schlegelii) fed a high fat diet. An 8-week feeding trial was conducted in black seabream with an initial weight of 8.39 ± 0.01g fed four isonitrogenous diets including Control, medium-fat diet (11%); HFD, high-fat diet (17%); and HFD supplemented with two levels (10 and 20 g/kg) of betaine, HFD+B1 and HFD+B2, respectively. SGR and FE in fish fed HFD+B2 were significantly higher than in fish fed HFD. Liver histology revealed that vacuolar fat droplets were smaller and fewer in bream fed HFD supplemented with betaine compared to fish fed HFD. Betaine promoted the mRNA and protein expression levels of silent information regulator 1 (Sirt1), up-regulated mRNA expression and protein content of lipid peroxisome proliferator-activated receptor alpha (pparα), and down-regulated mRNA expression and protein content of sterol regulatory element-binding protein-1(srebp-1). Furthermore, the mRNA expression levels of anti-inflammatory cytokines in liver and intestine were up-regulated, while nuclear factor kB (nf-kb) and pro-inflammatory cytokines were down-regulated by dietary betaine supplementation. Likewise, in fish that received lipopolysaccharide (LPS) to stimulate inflammatory responses, the expression levels of mRNAs of anti-inflammatory cytokines in liver, intestine and kidney were up-regulated in fish fed HFD supplemented with betaine compared with fish fed HFD, while nf-kb and pro-inflammatory cytokines were down-regulated. This is the first report to suggest that dietary betaine could be an effective feed additive to alleviate hepatic steatosis and attenuate inflammatory responses in black seabream fed a high fat diet by modulating the Sirt1/Srebp-1/Pparɑ pathway.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

scholarly journals Cystine reduces tight junction permeability and intestinal inflammation induced by oxidative stress in Caco-2 cells

Amino Acids ◽  
2021 ◽  
Author(s):  
Tatsuya Hasegawa ◽  
Ami Mizugaki ◽  
Yoshiko Inoue ◽  
Hiroyuki Kato ◽  
Hitoshi Murakami
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Whole Cells ◽  
Intestinal Barrier Dysfunction ◽  
Pro Inflammatory Cytokines

AbstractIntestinal oxidative stress produces pro-inflammatory cytokines, which increase tight junction (TJ) permeability, leading to intestinal and systemic inflammation. Cystine (Cys2) is a substrate of glutathione (GSH) and inhibits inflammation, however, it is unclear whether Cys2 locally improves intestinal barrier dysfunction. Thus, we investigated the local effects of Cys2 on oxidative stress-induced TJ permeability and intestinal inflammatory responses. Caco-2 cells were cultured in a Cys2-supplemented medium for 24 h and then treated with H2O2 for 2 h. We assessed TJ permeability by measuring transepithelial electrical resistance and the paracellular flux of fluorescein isothiocyanate–dextran 4 kDa. We measured the concentration of Cys2 and GSH after Cys2 pretreatment. The mRNA expression of pro-inflammatory cytokines was assessed. In addition, the levels of TJ proteins were assessed by measuring the expression of TJ proteins in the whole cells and the ratio of TJ proteins in the detergent-insoluble fractions to soluble fractions (IS/S ratio). Cys2 treatment reduced H2O2-induced TJ permeability. Cys2 did not change the expression of TJ proteins in the whole cells, however, suppressed the IS/S ratio of claudin-4. Intercellular levels of Cys2 and GSH significantly increased in cells treated with Cys2. Cys2 treatment suppressed the mRNA expression of pro-inflammatory cytokines, and the mRNA levels were significantly correlated with TJ permeability. In conclusion, Cys2 treatment locally reduced oxidative stress-induced intestinal barrier dysfunction possively due to the mitigation of claudin-4 dislocalization. Furthermore, the effect of Cys2 on the improvement of intestinal barrier function is related to the local suppression of oxidative stress-induced pro-inflammatory responses.

scholarly journals Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Awadhesh K. Arya ◽  
Kurt Hu ◽  
Lalita Subedi ◽  
Tieluo Li ◽  
Bingren Hu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Balloon Catheter ◽  
Organ Injury ◽  
Upper Body ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

scholarly journals Geongangbuja-Tang Decoction and Its Active Ingredient, Aconiti Lateralis Radix Preparata, Exerts Inhibitory Effects on Heat Stress-Induced Inflammation in Mice

2021 ◽  
Vol 11 (15) ◽  
pp. 6902
Author(s):  
Eugene Huh ◽  
Wonil Lee ◽  
Yujin Choi ◽  
Tae Hee Lee ◽  
Myung Sook Oh
Keyword(s):  
Heat Stress ◽  
Energy Metabolism ◽  
Inflammatory Cytokines ◽  
Hpa Axis ◽  
Inflammatory Responses ◽  
Heat Exposure ◽  
Mouse Serum ◽  
Dependent Manner ◽  
Active Constituent ◽  
Pro Inflammatory Cytokines

Heat stress induces the hypothalamic-pituitary-adrenal (HPA) axis activation, influences biological responses, and reduces energy metabolism. Geongangbuja-tang (GBT) and its components, Zingiberis Rhizoma (ZOR) and Aconiti Lateralis Radix Preparata (ALRP) have been used to induce energy metabolism; however, the effects of GBT and its ingredients on heat-induced inflammatory responses have not yet been investigated. In this study, we performed an open-field test to evaluate locomotor activity in mice. To assess the effects of GBT and its ingredients on inflammation, the protein levels of c-fos, pro-inflammatory cytokines, and cortisol were measured in the mouse hypothalamus and serum. The results showed that GBT alleviated locomotive activity and reduced c-fos levels in a dose-dependent manner under the heat exposure. After investigating the active constituent of GBT, we found that compared to GBT and ZOR, ALRP significantly suppressed c-fos expression under heat stress. Subsequently, ALRP decreased the expression of pro-inflammatory cytokines, such as interleukin-9 and -13 and prostaglandin, under the heat stress in the mouse hypothalamus. Moreover, treatment with ALRP inhibited cortisol secretion in the mouse serum following heat exposure. These results indicate that GBT and its active component, ALRP, could be the thermoregulatory agents that regulate the HPA axis.

scholarly journals Macrophage-Biomimetic Porous Se@SiO2 Nanocomposites For “Dual Model” Immunotherapy Against Inflammatory Osteolysis

2021 ◽  
Author(s):  
Cheng Ding ◽  
Chuang Yang ◽  
Tao Cheng ◽  
Xingyan Wang ◽  
Qiaojie Wang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Total Joint Replacement ◽  
Major Complication ◽  
Dual Model ◽  
Joint Replacement Surgery ◽  
Pro Inflammatory Cytokines ◽  
Macrophage Membrane

Abstract Background：Inflammatory osteolysis is a major complication of total joint replacement surgery that can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of pro-inflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (Porous Se@SiO2 nanospheres) for the management of inflammatory osteolysis. Results: Macrophage-membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) can attenuate lipopolysaccharide (LPS)-induced inflammatory osteolysis by a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduce toxin levels and neutralize pro-inflammatory cytokines. Moreover, the release of Se can induce the polarization of macrophages toward the anti-inflammatory M2-phenotype. These effects are mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase(ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduces the inhibition of osteogenic differentiation caused by pro-inflammation cytokines, confirmed through in vitro and in vivo experiments.Conclusion: Our findings suggest that M-Se@SiO2 has an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 is a promising engineered nano-platform for the treatment of osteolysis arising after arthroplasty.

scholarly journals Prolonged Helium Postconditioning Protocols during Early Reperfusion Do Not Induce Cardioprotection in the Rat HeartIn Vivo: Role of Inflammatory Cytokines

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Gezina Tanya Mei Ling Oei ◽  
Hamid Aslami ◽  
Raphaela Priscilla Kerindongo ◽  
Renske Johanna Steenstra ◽  
Charlotte Jacqueline Peter Beurskens ◽  
...  
Keyword(s):  
Infarct Size ◽  
Inflammatory Cytokines ◽  
Noble Gas ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Myocardial Tissue ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Early Reperfusion ◽  
Protein Levels

Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg) and diazepam (1.5 mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3) and interleukin-1 beta (IL-1β) were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

Abstract 316: Role of an Inflammasome Adaptor Molecule ASC (Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain) in Myocardial Ischemia-Reperfusion Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masanori Kawaguchi ◽  
Masafumi Takahashi ◽  
Takeki Hata ◽  
Yasuko Takahashi ◽  
Hajime Morimoto ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Caspase Recruitment Domain ◽  
Lv Dysfunction ◽  
Infarct Area ◽  
Injured Myocardium ◽  
Myocardial Ischemia Reperfusion

Inflammatory responses play a key role in the pathophysiology of myocardial ischemia-reperfusion (I/R) injury. ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) is an adaptor protein that forms “inflammasome” whose activation leads to caspase-1-dependent interleukin (IL)-1β generation and subsequent inflammatory responses; however, the role of ASC in myocardial I/R injury remains unclear. Baseline left ventricular (LV) function was unaltered in ASC-deficient (ASC −/− ) mice. ASC −/− (n=42) and wild-type control (WT) (n=42) mice were subjected to 30 min LAD occlusion, followed by reperfusion. ASC −/− mice showed reduced infarct area (infarct area/area at risk: 18.7% vs. 28.6% at 48 h, p< 0.01) and scar formation (scar/LV area: 9.7% vs. 14.6% at 14 days, p< 0.01) after myocardial I/R. Echocardiography showed improved LV dysfunction (%FS: 35.2 vs. 28.4 at 7 days, p< 0.01; 34.0 vs. 25.7 at 14 days, p< 0.01) and dimensions (LVEDD [mm]: 3.88 vs. 4.21 at 7 days, p< 0.01; 3.99 vs. 4.43 at 14 days, p< 0.01) in the ASC −/− mice after myocardial I/R. Immunohistochemistry revealed that infiltration of macrophages (Mac3) and neutrophils (Gr-1) was markedly decreased in the injured myocardium of the ASC −/− mice (48 hr [/mm 2 ]: 1226 vs. 884, p< 0.01; 782 vs. 554, p< 0.01, respectively); however, there was no difference of neovascularization (CD31) in the ischemic area. Double immunofluorescent staining showed that ASC expression was clearly observed in the infiltrated macrophages and neutrophils in the injured myocardium. Real-time RT-PCR analysis demonstrated that the myocardial expression of inflammatory cytokines, such as IL-1β, IL-6, and MCP-1, after I/R were significantly decreased in the ASC −/− mice, compared to that in the WT mice. Further, in vitro experiments showed that LPS-induced production of these inflammatory cytokines in the ASC −/− bone marrow cells was significantly decreased. These findings demonstrate that ASC deficiency prevents inflammatory cell infiltration and cytokine expression, thereby resulting in the improvement of LV dysfunction and remodeling after myocardial I/R injury, and suggest that ASC is a novel therapeutic target for myocardial I/R injury.

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