Beneficial effects of edaravone in experimental model of amitriptyline-induced cardiotoxicity in rats

Başol, Nurşah; Aygün, Hatice; Gül, Serdar

doi:10.1007/s00210-019-01683-6

Cited by 11 publications

(11 citation statements)

References 29 publications

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“…21,22 Edaravone (ED; 3-methyl-1-phenyl-2-pyrazolin-5-one) is a low molecular weight agent with potent radical-scavenging properties that protect the cells from death. 23 ED has a neuroprotective activity mediated via its ability to suppress oxidative stress, 24,25 and protected against bleomycin-induced lung injury 26 and amitriptyline-induced cardiotoxicity 27 in murine models. Given the potent antioxidant properties of AV and ED, this study explored their protective effect against CP cardiotoxicity, pointing to the possible involvement of PI3K/ Akt/mTOR and Nrf2 signaling.…”

Section: Introductionmentioning

confidence: 99%

<p>Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats</p>

Hassanein

El-Ghafar

Ahmed

et al. 2020

DDDT

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Introduction: Cyclophosphamide (CP) causes redox imbalance and its use is associated with marked cardiotoxicity that limits its clinical applications. The present study investigated the protective effects of acetovanillone (AV) and edaravone (ED) against CP-induced oxidative stress and cardiac damage, emphasizing the role of PI3K/Akt/mTOR and Nrf2 signaling. Materials and Methods: Rats received either AV (100 mg/kg) or ED (20 mg/kg) orally for 10 days and CP (200 mg/kg) on day 7. At day 11, the rats were sacrificed, and samples were collected for analysis. Results: AV and ED ameliorated serum troponin I, CK-MB, LDH, AST and ALP, and prevented cardiac histological alterations in CP-intoxicated rats. Both treatments decreased cardiac lipid peroxidation and enhanced GSH, SOD and cytoglobin in CP-induced rats. AV and ED downregulated Keap1, whereas increased the expression of PI3K, Akt, mTOR and Nrf2 in the heart of rats received CP. Additionally, the binding modes of AV and ED to Keap1 were pinpointed in silico using molecular docking simulations. Conclusion: AV and ED prevent CP cardiotoxicity by attenuating oxidative stress and tissue injury, and modulating cytoglobin, and PI3K/Akt/mTOR and Keap1/Nrf2 signaling. Therefore, AV and ED may represent promising agents that can prevent cardiac injury in patients receiving CP.

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Section: Introductionmentioning

confidence: 99%

<p>Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats</p>

Hassanein

El-Ghafar

Ahmed

et al. 2020

DDDT

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“…erefore, effective treatment programs to improve the ADL of patients have become the key to improving the prognosis of the disease [24]. In this study, it was found that the modified Barthel score after treatment was obviously higher in ACI patients who received edaravone combined with anticoagulant therapy than in those with routine treatment, indicating that the combined therapy can reduce perfusion injury of cerebral cells and improve the ADL of patients.…”

Section: Discussionmentioning

confidence: 66%

Effect of Edaravone Combined with Anticoagulant Therapy on the Serum hs-CRP, IL-6, and TNF-α Levels and Activity of Daily Living in Patients with Acute Cerebral Infarction

Sun

et al. 2022

Journal of Healthcare Engineering

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Objective. To explore the effect of edaravone combined with anticoagulant therapy on the serum hs-CRP, IL-6, and TNF-α levels and the activity of daily living (ADL) in patients with acute cerebral infarction (ACI). Methods. The clinical data of 84 ACI patients treated in our hospital from August 2020 to August 2021 were retrospectively analyzed, and they were divided into the routine group (n = 42) and the combined group (n = 42) according to the order of admission. Both groups were treated with routine clinical treatment, and the combined group was additionally treated with edaravone combined with anticoagulant therapy. Serum samples were collected from both groups after treatment. ELISA was used to detect the serum inflammatory factor levels, and the modified Barthel index score was used to evaluate the ADL of patients. Results. Compared with the routine group, the combined group achieved obviously lower levels of PMA, CD62p, and serum inflammatory factors after treatment ( P < 0.001 ), higher modified Barthel score after treatment ( P < 0.001 ), lower plasma viscosity, platelet aggregation rate, and plasma fibrinogen level after treatment ( P < 0.001 ), and higher clinical overall efficacy ( P < 0.05 ). Conclusion. Edaravone combined with anticoagulant therapy is a reliable method to enhance ADL and reduce the inflammatory response of ACI patients. This strategy greatly reduces the platelet-activating factor levels of patients and improves the comprehensive clinical efficacy, and its further research will help to establish a better solution for these patients.

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“…The antioxidant efficacy of ED has been previously reported in rodent models of neurologic disorders, [ 16,17 ] lung injury, [ 18 ] and cardiotoxicity. [ 19 ] Owing to the role of oxidative stress in CP toxicity, it is noteworthy assuming that attenuation of redox imbalance is involved in the ameliorative effect of ED.…”

Section: Discussionmentioning

confidence: 99%

“…[ 14,15 ] ED protected against oxidative stress in animal models of neurologic disorders, [ 16,17 ] lung injury, [ 18 ] and cardiotoxicity. [ 19 ] The amphiphilic capacity of ED permits its distribution in both hydrophilic and lipophilic conditions. [ 20 ] The ability of ED to scavenge free radicals might be mediated via its electron‐donating properties.…”

Section: Introductionmentioning

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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Beneficial effects of edaravone in experimental model of amitriptyline-induced cardiotoxicity in rats

Cited by 11 publications

References 29 publications

<p>Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats</p>

<p>Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats</p>

Effect of Edaravone Combined with Anticoagulant Therapy on the Serum hs-CRP, IL-6, and TNF-α Levels and Activity of Daily Living in Patients with Acute Cerebral Infarction

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

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