Inhibitory effect of edaravone on systemic inflammation and local damage in skeletal muscles following long-term ischemia to murine hind limb

Yokoyama, Hirokazu; Tsujii, Masaya; Iino, Takahiro; Nakamura, Tomoki; Sudo, Akihiro

doi:10.1177/2309499019874470

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…[ 55 ] ED supplementation suppressed TLR‐4/NF‐κB signaling, TNF‐ α , and IL‐6 and increased IL‐10 and iKK β in the urinary bladder of CP‐intoxicated rats, demonstrating a potent anti‐inflammatory activity. Accordingly, numerous studies showed that the protective effect of ED against liver, [ 56 ] lung, [ 57 ] and skeletal muscle [ 58 ] injuries were associated with the inhibition of NF‐κB. This inhibitory activity of ED was further explored using molecular docking simulation, which showed its ability to bind to TLR‐4 and NF‐κB.…”

Section: Discussionmentioning

confidence: 99%

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR‐4/NF‐κB, and JAK1/STAT3 signaling in cyclophosphamide‐intoxicated rats

Hassanein

Ahmed

Sayed

et al. 2021

J Biochem & Molecular Tox

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Hemorrhagic cystitis is a potentially deadly complication associated with radiation therapy and chemotherapy. This study explored the protective effect of edaravone (ED) on cyclophosphamide (CP)‐induced hemorrhagic cystitis, oxidative stress, and inflammation in rats. The animals received 20 mg/kg ED for 10 days and a single injection of 200 mg/kg CP on day 7. CP induced tissue injury manifested by the diffuse necrotic changes, disorganization of lining mucosa, focal hemorrhagic patches, mucosal/submucosal inflammatory cells infiltrates, and edema. CP increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor‐alpha, and interleukin 6 (IL‐6), decreased IL‐10, and upregulated toll‐like receptor 4 (TLR‐4), nuclear factor‐kappa B (NF‐κB) p65, Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) in the urinary bladder of rats. ED effectively prevented the histopathological alterations, decreased MDA, NO, and inflammatory mediators, and downregulated TLR‐4, NF‐κB, JAK1, and STAT3 in CP‐induced rats. Treatment with ED upregulated ikβ kinase β, IL‐10, nuclear factor‐erythroid 2 related factor 2 (Nrf2), and cytoglobin, and boosted glutathione, superoxide dismutase, and glutathione S‐transferase. Molecular docking simulations revealed the ability of ED to bind TLR‐4, NF‐κB, JAK1, and STAT3. In vitro, ED increased the cytotoxic activity of CP against HeLa, Caco‐2, and K562 cell lines. In conclusion, ED prevented CP‐induced hemorrhagic cystitis in rats by attenuating oxidative stress, suppressing TLR‐4/NF‐κB, and JAK1/STAT3 signaling and boosted Nrf2, cytoglobin, and antioxidants.

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Section: Discussionmentioning

confidence: 99%

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR‐4/NF‐κB, and JAK1/STAT3 signaling in cyclophosphamide‐intoxicated rats

Hassanein

Ahmed

Sayed

et al. 2021

J Biochem & Molecular Tox

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“…The HO-1, NQO1 and SOD are protective proteins against oxidative stress, and MDA is a common product of oxidative stress. 37,38 HO-1 functions as an important protein of cell adaptation to oxidative stress by generating carbon monoxide, biliverdin and free iron. 39 NQO1 is a type of cytosolic flavoprotein, which can transfer electrons, 40 hydroquinones.…”

Section: Discussionmentioning

confidence: 99%

Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway‐mediated enhancement of autophagy

Qin

Zhao³

et al. 2023

International Wound Journal

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Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia–reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy‐related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7 days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3‐methyladenine (3‐MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3‐MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA‐induced autophagy was mediated through downregulating PI3K/Akt/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K/AKT/mTOR signalling pathway.

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“…29) On the other hand, the intestinal mucosal barrier injury caused by AP can cause intestinal conditions pathogenic bacteria to shift into the blood circulation, and the resulting exogenous ligands are recognized by TLR4, start the NFκB pathway, and up-regulate the expressions of inflammatory mediators such as cytokines and chemokines. 30) Some studies show that the protective effect of edaravone against acute lung injury, 31) skeletal muscles, 32) acute kidney injury 33) and acute stroke 34) associated with the NFκB activation and inflammatory cytokine production. In addition, other studies point to EDA inhibition of mRNA levels of TLR4 and NFκB expression in cerebral ischemia-reperfusion in mice.…”

Section: Discussionmentioning

confidence: 99%

Edaravone Protects against Pancreatic and Intestinal Injury after Acute Pancreatitis <i>via</i> Nuclear Factor-κB Signaling in Mice

Wang

Lin

2020

Biological & Pharmaceutical Bulletin

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Acute pancreatitis (AP) is one kind of acute surgical abdominal disease in the world. It causes intestinal damage with subsequent bacterial migration, endotoxemia and secondary pancreatic infections. In this investigation, we determined that edaravone (EDA) reduces pancreatic and intestinal injury after AP in mice. This was demonstrated by a reduction in histological score, apoptosis, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, along with obstructing activation of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NFκB). Our study results suggested that EDA exerts its protective effects against pancreatic and intestinal injury after AP via regulation of the TLR4/NFκB pathway. Our findings provide the basis for EDA to treat AP-induced pancreatic and intestinal injury, even might develop as a potential therapy for other inflammatory diseases.

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Inhibitory effect of edaravone on systemic inflammation and local damage in skeletal muscles following long-term ischemia to murine hind limb

Cited by 10 publications

References 36 publications

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR‐4/NF‐κB, and JAK1/STAT3 signaling in cyclophosphamide‐intoxicated rats

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR‐4/NF‐κB, and JAK1/STAT3 signaling in cyclophosphamide‐intoxicated rats

Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway‐mediated enhancement of autophagy

Edaravone Protects against Pancreatic and Intestinal Injury after Acute Pancreatitis <i>via</i> Nuclear Factor-κB Signaling in Mice

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