scholarly journals Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 7894 ◽  
Author(s):  
Il-Gyu Ko ◽  
Jun-Jang Jin ◽  
Lakkyong Hwang ◽  
Sang-Hoon Kim ◽  
Chang-Ju Kim ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Inflammatory Cytokines ◽  
Intraperitoneal Injection ◽  
Acute Liver Injury ◽  
Adenosine A2a Receptor ◽  
Liver Index ◽  
A2a Receptor ◽  
Adenosine A2a ◽  
Pro Inflammatory Cytokines

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 μL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

A selective adenosine A2A receptor agonist, ATL-146e, prevents concanavalin A-induced acute liver injury in mice

2006 ◽  
Vol 347 (4) ◽  
pp. 949-954 ◽  
Author(s):  
Masaru Odashima ◽  
Michiro Otaka ◽  
Mario Jin ◽  
Youhei Horikawa ◽  
Tamotsu Matsuhashi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Concanavalin A ◽  
Receptor Agonist ◽  
Acute Liver Injury ◽  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals Platycodon grandiflorus Fermented Extracts Attenuate Endotoxin-Induced Acute Liver Injury in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2802
Author(s):  
So Ra Kim ◽  
Eun Jung Park ◽  
Theodomir Dusabimana ◽  
Jihyun Je ◽  
Kyuho Jeong ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Cytokines ◽  
Acute Liver Injury ◽  
Pharmacological Action ◽  
Hepatic Necrosis ◽  
Raw264.7 Cells ◽  
Anti Inflammatory ◽  
High Doses ◽  
Pharmacologically Active ◽  
Pro Inflammatory Cytokines

Endotoxin-induced acute liver injury is mediated by an excessive inflammatory response, hepatocellular oxidative stress, and apoptosis. Traditional medicinal plants have been used to treat various disorders. Platycodon grandifloras (PG) has been shown to be beneficial in relieving cough and asthma and to have anti-tumor, anti-inflammatory, anti-diabetic activities. The pharmacological action of PG is mainly due to saponins, flavonoids, phenolic, and other compounds. However, raw PG exhibits some side effects at high doses. Here, we extracted raw PG with varying fermentation methods and examined its anti-inflammatory effect and associated signaling kinases in Raw264.7 cells. Then, we investigated the effect of fermented black PG (FBPG) on endotoxin-induced liver injury. Mice were administered FBPG orally at 1 h before the lipopolysaccharide and D-galactosamine (LPS/GalN) injection and sacrificed after 5 h. Black PG (BPG) and FBPG showed a significant reduction in pro-inflammatory cytokines and extracellular nitric oxide (NO); p-38 and ERK signaling was involved in reducing inducible NO synthase in Raw264.7 cells. Consistently, FBPG attenuates LPS/GalN-induced liver injury; plasma ALT and AST, hepatic necrosis, pro-inflammatory cytokines, apoptosis, and lipid peroxidation were all reduced. In conclusion, PG extracts, particularly FBPG, play anti-inflammatory, antioxidant, and anti-apoptotic roles, alleviating endotoxin-induced acute liver injury. Processing raw PG into FBPG extract may be clinically useful by improving the pharmacologically active ingredients and reducing the required dosage.

scholarly journals Puerarin Prevents Acute Liver Injury via Inhibiting Inflammatory Responses and ZEB2 Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Junfa Yang ◽  
Maomao Wu ◽  
Hui Fang ◽  
Yue Su ◽  
Lingling Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Zeb2 Expression ◽  
Pro Inflammatory Cytokines

Puerarin, an isoflavone component extracted from herb radix puerariae, is widely used in China in the treatment of immune diseases and inflammation. Previous studies have demonstrated that puerarin prevented acute lung injury by regulating inflammatory responses. However, the effect of puerarin on acute liver injury (ALI) was unclear. The purpose of this study was to explore the beneficial effects of puerarin when applied to ALI. We found that puerarin inhibited liver injury and inflammatory cell infiltration in lipopolysaccharide (LPS)/D-galactose (D-Gal)-induced acute liver failure and the liver pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in liver tissues with ALI and LPS-induced L-02 cells but upregulated the expression level of zinc finger E-box-binding homeobox 2 (ZEB2). Significantly, the results of this study showed that the inhibition of liver pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) production in LPS-induced L-02 cells was caused by ZEB2 overexpression. However, knocking down ZEB2 promoted LPS-mediated secretion of liver pro-inflammatory cytokines in L-02 cells. Additional experiments showed that puerarin inhibited the activation of the NF-κB signaling pathway by elevating ZEB2 expression in L-02 cells. In summary, puerarin most likely prevented activation of the pro-inflammatory factors and reduced LPS/D-Gal-induced liver injury by enhancing the ZEB2 expression level and, consequently, blocking activation of the NF-κB signaling pathway in the liver.

scholarly journals The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Su-Zhi Xie ◽  
Xiang-Yang Zhai ◽  
Sheng-Yan Xi ◽  
Ying-Kun Qiu ◽  
Yu-Mei Zhang ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Protein Expression ◽  
Liver Tissue ◽  
Intraperitoneal Injection ◽  
Acute Liver Injury ◽  
Peanut Oil ◽  
Protective Effects ◽  
Liver Index ◽  
Tnf Α

Background:Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI).Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms.Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined.Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1β, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI.Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.

Synthesis of the Adenosine A2A Receptor Fluorescent Agonist MRS5424

BIO-PROTOCOL ◽  
2014 ◽  
Vol 4 (6) ◽  
Author(s):  
Kenneth Jacobson ◽  
Francisco Ciruela
Keyword(s):  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a

Optimization of the Human Adenosine A2a Receptor Yields in Saccharomyces cerevisiae

2008 ◽  
Vol 22 (5) ◽  
pp. 1249-1255 ◽  
Author(s):  
Alison Wedekind ◽  
Michelle A. O'Malley ◽  
Ronald T. Niebauer ◽  
Anne S. Robinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals A Cellular Assay for the Identification and Characterization of Connexin Gap Junction Modulators

2021 ◽  
Vol 22 (3) ◽  
pp. 1417
Author(s):  
Azeem Danish ◽  
Robin Gedschold ◽  
Sonja Hinz ◽  
Anke C. Schiedel ◽  
Dominik Thimm ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
High Throughput Screening ◽  
Cell Communication ◽  
Receptor Activation ◽  
Adenosine A2a Receptor ◽  
Intracellular Camp ◽  
Donor Cells ◽  
A2a Receptor ◽  
Adenosine A2a

Connexin gap junctions (Cx GJs) enable the passage of small molecules and ions between cells and are therefore important for cell-to-cell communication. Their dysfunction is associated with diseases, and small molecules acting as modulators of GJs may therefore be useful as therapeutic drugs. To identify GJ modulators, suitable assays are needed that allow compound screening. In the present study, we established a novel assay utilizing HeLa cells recombinantly expressing Cx43. Donor cells additionally expressing the Gs protein-coupled adenosine A2A receptor, and biosensor cells expressing a cAMP-sensitive GloSensor luciferase were established. Adenosine A2A receptor activation in the donor cells using a selective agonist results in intracellular cAMP production. The negatively charged cAMP migrates via the Cx43 gap junctions to the biosensor cells and can there be measured by the cAMP-dependent luminescence signal. Cx43 GJ modulators can be expected to impact the transfer of cAMP from the donor to the biosensor cells, since cAMP transit is only possible via GJs. The new assay was validated by testing the standard GJ inhibitor carbenoxolon, which showed a concentration-dependent inhibition of the signal and an IC50 value that was consistent with previously reported values. The assay was demonstrated to be suitable for high-throughput screening.

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