scholarly journals Beneficial Effect of Dimethyl Fumarate on Experimental Autoimmune Uveitis is Dependent of Pro-Inflammatory Markers Immunomodulation

2021 ◽  
Author(s):  
Chafia TOUIL-BOUKOFFA ◽  
Moussa Labsi ◽  
Imene Soufli ◽  
Houda Belguendouz ◽  
Sara Djebbara ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Tap Water ◽  
Control Group ◽  
Histological Structure ◽  
Intragastric Administration ◽  
Autoimmune Uveitis ◽  
Experimental Autoimmune Uveoretinitis ◽  
Tnf Α ◽  
Experimental Autoimmune

Abstract Autoimmune uveitis is an inflammatory disease of the eye and is one of the major causes of blindness worldwide. Experimental autoimmune uveoretinitis (EAU) constitutes an animal disease model of human endogenous uveitis. In our study, we investigated the immunomodulatory effect of Dimethylfumarate (DMF) using bovine retinal extract-induced uveitis in a Female Wistar rats. To evaluate the in vivo efficacy, Female Wistar rats were divided into 7 experimental groups: control group (n = 5), consisting of non-immunized animals; Uveoretinitis (n = 5), and DMF/Uveoretinitis groups (n = 15), which received a subcutaneous injection of bovine retinal extract emulsified in complete Freund’s adjuvant; MC group (n = 5), treated by daily intragastric administration of methylcellulose 0.08% in tap water; DMF group, consisting of control positive group, rats received daily oral gavage administration of 500 µL of Dimethylfumarate at 100mg/Kg dissolved in 0.08% methylcellulose in tap water (n = 5). On days 14 post immunization, the rats were then euthanized and associated indications were investigated to evaluate the therapeutic efficacy. Nitric oxide (NO) and TNF-α were assessed in plasma. Meanwhile, eyes were collected for histological and immunohistochemical studies. The retinal expression of iNOS, CD68, CD20, CD25, CD4, and CD8 was examined. Interestingly, DMF enhanced a significant reduction of NO and TNF-α production in the treated group. This effect was strongly related to the histological structure of eyes improvement. In the same context, a significant decrease of iNOS, CD68, and CD20 expression and CD25 increase expression were reported in retinal tissue of DMF/Uveoretinitis group in comparison to the immunized group. Collectively, our results indicate that DMF treatment has a beneficial effect in experimental autoimmune uveoretinitis and could constitute a good candidate for monitoring an ocular inflammatory diseases.

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

Beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia in apolipoprotein E-deficient mice

2008 ◽  
Vol 86 (12) ◽  
pp. 815-826 ◽  
Author(s):  
Hong-Bo Xiao ◽  
Zhi-Liang Sun ◽  
Xiang-Yang Lu ◽  
Da-Zhi Li ◽  
Jian-Ping Xu ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Apolipoprotein E ◽  
Density Lipoprotein ◽  
Control Group ◽  
Elevated Expression ◽  
Plasma High Density ◽  
Adipose Tissue Lipoprotein Lipase ◽  
Xanthone Compound

Previous investigations have shown that decreased expression of angiopoietin-like protein 3 (Angptl3) is protective against dyslipidemia in atherosclerosis. The present study was conducted to test the effect of 3,4,5,6-tetrahydroxyxanthone, a xanthone compound, on dyslipidemia in apolipoprotein E-deficient (ApoE−/−) mice. Forty mice were randomly divided into 4 groups (n = 10): control group (C57BL/6J mice), ApoE−/− mice group, and two groups of ApoE−/− mice treated with 3,4,5,6-tetrahydroxyxanthone (10 or 30 mg/kg per day). Eight weeks after treatment, lipid levels in the blood and liver, expression of hepatic Angptl3, and adipose tissue lipoprotein lipase (LPL) were determined. Treatment with 3,4,5,6-tetrahydroxyxanthone (10 or 30 mg/kg) significantly decreased plasma and hepatic total cholesterol and triglyceride concentrations, increased plasma high-density lipoprotein cholesterol, and significantly downregulated expression of Angptl3 mRNA and protein concomitantly with upregulated expression of LPL mRNA. In addition, T0901317 (a liver X receptor ligand) caused elevated expression of hepatic Angptl3 mRNA and protein, and the effect of T0901317 was also abrogated by 3,4,5,6-tetrahydroxyxanthone in vivo and in vitro. The present results suggest that the beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia may be related to reduced expression of Angptl3.

scholarly journals In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 478 ◽  
Author(s):  
Rasha Al-Rikabi ◽  
Hanady Al-Shmgani ◽  
Yaser Hassan Dewir ◽  
Salah El-Hendawy
Keyword(s):  
Breast Cancer ◽  
Chromatin Condensation ◽  
Control Group ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mcf7 Cells ◽  
Tnf Α

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.

In vivo leucocyte dynamics experimental autoimmune uveoretinitis

1997 ◽  
Vol 56 ◽  
pp. 207
Author(s):  
Graham Wallace ◽  
Adrian Pamaby-Price ◽  
Roy Whiston ◽  
Miles Stanford
Keyword(s):  
Experimental Autoimmune Uveoretinitis ◽  
Experimental Autoimmune

Chronically Administered Acetaminophen and the Ischemia/Reperfused Myocardium

2003 ◽  
Vol 228 (6) ◽  
pp. 674-682 ◽  
Author(s):  
R. Golfetti ◽  
T. Rork ◽  
G. Merrill
Keyword(s):  
Creatine Kinase ◽  
Tap Water ◽  
Chronic Administration ◽  
Left Ventricular ◽  
Low Flow ◽  
Control Group ◽  
Coronary Perfusion ◽  
In Vitro Production

Male and female Hartley strain guinea pigs weighing 280 ± 10 g were given acetaminophen-treated water ad libitum for 10 days. Sham-treated control animals were given similar quantities of untreated tap water (vehicle-treated control group). On Day 10, hearts were extracted, instrumented, and exposed to an ischemia (low-flow, 20 min)/reperfusion protocol. Our objective was to compare and contrast ventricular function, coronary circulation, and selected biochemical and histological indices in the two treatment groups. Left ventricular developed pressure in the early minutes of reperfusion was significantly greater in the presence of acetaminophen, e.g., at 1 min, 40 ± 4 vs 21 ± 3 mmHg ( P < 0.05). Coronary perfusion pressure was significantly less from 3 to 40 min of reperfusion in the presence of acetaminophen. Creatine kinase release in vehicle-treated hearts rose from 42 ± 14 (baseline) to 78 ± 25 units/liter by the end of ischemia. Corresponding values in acetaminophen-treated hearts were 36 ± 8 and 44 ± 14 units/liter. Acetaminophen significantly ( P < 0.05) attenuated release of creatine kinase. Chemiluminescence, an indicator of the in vitro production of peroxynitrite via the in vivo release of superoxide and nitric oxide, was also significantly attenuated by acetaminophen. Electron microscopy indicated a well-preserved myofibrillar ultrastructure in the postischemic myocardium of acetaminophen-treated hearts relative to vehicle-treated hearts (e.g., few signs of contraction bands, little or no evidence of swollen mitochondria, and well-defined light and dark bands in sarcomeres with acetaminophen; opposite with vehicle). We conclude that chronic administration of acetaminophen provides cardioprotection to the postischemic, reperfused rodent myocardium.

scholarly journals Blockade of NF-κB and MAPK pathways by ulinastatin attenuates wear particle-stimulated osteoclast differentiation in vitro and in vivo

2016 ◽  
Vol 36 (5) ◽  
Author(s):  
Jiang-Ying Ru ◽  
Hai-Dong Xu ◽  
Dai Shi ◽  
Jun-Bo Pan ◽  
Xiao-Jin Pan ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Treated Group ◽  
Receptor Activation ◽  
Raw264.7 Cells ◽  
Control Group ◽  
Nuclear Factor ◽  
Trabecular Thickness ◽  
Tnf Α

Ulinastatin, a urinary trypsin inhibitor (UTI), is widely used to clinically treat lipopolysaccharide (LPS)-related inflammatory disorders recently. Adherent pathogen-associated molecular patterns (PAMPs), of which LPS is the best-studied and classical endotoxin produced by Gram-negative bacteria, act to increase the biological activity of osteopedic wear particles such as polymethyl-methacrylate (PMMA) and titanium particles in cell culture and animal models of implant loosening. The present study was designed to explore the inhibitory effect of UTI on osteoclastogenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw264.7 cells and murine osteolysis models, and investigate the potential mechanism. The in vitro study was divided into the control group, LPS-induced group, PMMA-stimulated group and UTI-pretreated group. UTI (500 or 5000 units/ml) pretreatment was followed by PMMA (0.5 mg/ml) with adherent LPS. The levels of inflammatory mediators including tumour necrosis factor-α (TNF-α), matrixmetallo-proteinases-9 (MMP-9) and interleukin-6 (IL-6), receptor activation of nuclear factor NF-κB (RANK), and cathepsin K were examined and the amounts of phosphorylated I-κB, MEK, JNK and p38 were measured. In vivo study, murine osteolysis models were divided into the control group, PMMA-induced group and UTI-treated group. UTI (500 or 5000 units/kg per day) was injected intraperitoneally followed by PMMA suspension with adherent LPS (2×108 particles/25 μl) in the UTI-treated group. The thickness of interfacial membrane and the number of infiltrated inflammatory cells around the implants were assessed, and bone mineral density (BMD), trabecular number (Tb.N.), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), relative bone volume over total volume (BV/TV) of distal femur around the implants were calculated. Our results showed that UTI pretreatment suppressed the secretion of proinflammatory cytokines including MMP-9, IL-6, TNF-α, RANK and cathepsin K through down-regulating the activity of nuclear factor kappa B (NF-κB) and MAPKs partly in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In conclusion, these results confirm the anti-inflammatory potential of UTI in the prevention of particle disease.

The Effects of Moxibustion on Serum Interleukins and T Cell Subset in H.polyri Infected Rats

2015 ◽  
Vol 3 (1) ◽  
pp. 38-45
Author(s):  
Jing Shen ◽  
Yan Peng ◽  
Dong-Mei Shi ◽  
Yin-Shuai Feng ◽  
Yan-Ling Hou ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Control Group ◽  
Intragastric Administration ◽  
Therapeutic Effects ◽  
Model Group ◽  
Tnf Α ◽  
Group A ◽  
Histomorphological Changes ◽  
Group B ◽  
Group D

Abstract Objective: to observe the effects of moxibustion on histomorphological changes of gastric mucosa, as well as on serum IL-6、IL-8、TNF-α，Hp IgG、CD3+、CD4+、CD8+ in helicobacter pylori (Hp) infected rats, so that to better understand how the moxibustion repairs the Hp- induced gastric mucosal injury. Methods: 40 SD rats were randomly assigned to four groups: group A (blank control), group B (Hp infection model), group C (moxibustion plus model), group D (electro-acupuncture plus model), 10 for each group. The “NaHCO3 plus Indometacin and Hp intragastric administration” method was employed to make gastritis model. Acupoints selected for “repair” purpose were Zu San Li (ST36), Zhong Wan (CV12), Guan Yuan (RN4), Pi Shu (BL20), Wei Shu(BL21). The histomorphological changes of gastric mucosa in rats were observed under light microscope after HE stain; IL-6, IL-8, TNF-α, Hp IgG values were evaluated by ELISA method; values of CD3+、CD4+、CD8+、CD4+/CD8+ were measured by flow cytometry method. Results: compared with group A, the values of IL-6, IL-8, TNF-α, Hp IgG and CD8+ in group B were increased（P＜0.01）, whereas the values of CD3+、CD4+、CD4+/CD8+ were decreased（P＜0.01）. Compared with group B, the values of IL-8（P＜0.05）,TNF-α（P＜0.05）, IL-6（P＜0.01）, Hp IgG（P＜0.01） and CD8+ （P＜0.05） in group C were decreased, whereas the values of CD3+（P＜0.05）,CD4+（P＜0.05）,CD4+/CD8+ （P＜0.05） were increased, meanwhile such values in group D had no significant changes. Compared with group D, the values of IL-6（P＜0.05）,IL-8 （P＜0.05）and Hp IgG （P＜0.01）in group C were decreased, whereas CD4+/CD8+（P＜0.05）were increased, all those changes had statistical significance. Conclusion: the preventive and therapeutic effects of moxibustion on Hp related gastritis might be realized by two ways- to inhibit the secretion of proinflammatory cytokines such as IL-6, IL-8 and TNF-α, or to regulate the production of immune factors (such as up-regulation of CD3+, CD4+ and down-regulation of CD8+).

scholarly journals Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo

2017 ◽  
Vol 44 (6) ◽  
pp. 2395-2406 ◽  
Author(s):  
Li-yun Pan ◽  
Ya-feng Chen ◽  
Hong-chang Li ◽  
Li-ming Bi ◽  
Wen-jie Sun ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Serum Amylase ◽  
Endothelial Damage ◽  
Intestinal Injury ◽  
Control Group ◽  
Rt Pcr ◽  
Intestinal Tissue ◽  
Tnf Α

Background/Aims: Dachengqi decoction (DCQD) is a well-known traditional Chinese herbal drug with strong anti-inflammatory effects. Angiopoietin-1 (Ang-1) plays a vital role in maintaining the stability and integrity of the vascular wall and prevents vascular leakage due to inflammatory mediators. Our previous work found that DCQD protects against pancreatic injury in rats with severe acute pancreatitis (SAP). This study aims to investigate the effects of DCQD on intestinal endothelial damage in both damaged human umbilical vein endothelial cells (HUVECs) and SAP rats. Methods: HUVECs were randomly divided into four groups: control group, TNF-α group, TNF-α plus Ang-1 group (Ang-1 group), and TNF-α plus DCQD group (DCQD group). Cells were incubated for 6 h, 12 h, and 24 h, before collection. The treatment concentration of DCQD was decided based on a Cell Counting Kit-8 (CCK-8) assay. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TEER). Apoptosis was analyzed by flow cytometry. mRNA and protein expression of aquaporin 1 (AQP-1), matrix metalloproteinase 9 (MMP9), and junctional adhesion molecule-C (JAM-C) was evaluated by RT-PCR, immunocytofluorescence, and western blot. Forty male Sprague-Dawley rats were randomized into a control group, SAP group, SAP plus Ang-1 group (Ang-1 group), and SAP plus DCQD group (DCQD group). SAP was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS), while the control group received 0.9% saline solution. Evans blue was injected through the penile vein and the rats were then sacrificed 12 h after modeling. Levels of serum amylase, TNF-α, IL-1β, IL-2, and IL-6 were determined by using ELISA. Intestinal tissue was analysed by histology, and capillary permeability in the tissues was evaluated by Evans blue extravasation assay. Protein and mRNA expression of AQP-1, MMP9, and JAM-C were assessed by immunohistofluorescence, western blot, and RT-PCR. Results: DCQD reduced the permeability of HUVEC induced by TNF-α in vitro. Furthermore, DCQD altered the mRNA and protein levels of JAM-C, MMP9, and AQP-1 in HUVECs after TNF-α induction. SAP intestinal injury induced by cerulein combined with lipopolysaccharides was concomitant with increased expression of JAM-C and MMP9, and reduced expression of AQP-1 in intestinal tissue. Pretreatment with DCQD attenuated SAP intestinal injury and lowered the levels of serum amylase, TNF–α, IL-1β, IL-2, and IL-6 effectively. Our study demonstrated that DCQD decreased the expression of JAM-C and MMP9 and increased the expression of AQP-1 both in vitro and in vivo. Conclusion: DCQD can reduce capillary endothelial damage in acute pancreatitis-associated intestinal injury and the mechanism may be associated with the regulation of endothelial barrier function-associated proteins AQP-1, MMP9, and JAM-C.

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