Edaravone and benidipine protect myocardial damage by regulating mitochondrial stress, apoptosis signalling and cardiac biomarkers against doxorubicin-induced cardiotoxicity

Hassan, Quamrul; Akhtar, Sayeed; Afzal, Obaid; Hussain, Ibraheem; Akhtar, Mohd; Haque, Syed Ehtaishamul; Najmi, Abul Kalam

doi:10.1080/10641963.2019.1676770

Cited by 20 publications

(12 citation statements)

References 43 publications

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“…Group‐I animals served as control. Group‐II and ‐III animals were administered with the 2.5 mg/kg doxorubicin each alternate day for 14 days 23 . Furthermore, Group‐III animals were supplemented orally with the 50 mg/kg plumbagin.…”

Section: Methodsmentioning

confidence: 99%

Plumbagin protects the myocardial damage by modulating the cardiac biomarkers, antioxidants, and apoptosis signaling in the doxorubicin‐induced cardiotoxicity in rats

Chinnathambi

Alharbi

et al. 2020

Environmental Toxicology

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Cardiovascular disease created enormous health and economic burdens worldwide, which is responsible for the highest mobility and mortality that results in nearly 6.2% of in‐hospital deaths every year. Plumbagin is a major bioactive compound that occurs in the Plumbago indica and P. zeylanica with numerous therapeutic benefits. The current research exploration was planned to investigate the therapeutic role of plumbagin against doxorubicin stimulated cardiotoxicity in rats. The cardiotoxicity was stimulated to the rats by administering the 2.5 mg/kg of doxorubicin for 14 days with concurrent supplementation with plumbagin. The hemodynamic parameters were studied by using the tail‐cuff plethysmography. The lipid peroxidation and antioxidant status was examined by the standard procedures. The myocardial function and damage markers were assessed with the help of commercial kits. The expression status of inflammatory markers and PI3K/Akt signaling markers were investigated by reverse transcription polymerase chain reaction (RT‐PCR) and western blotting analysis, respectively. The plumbagin supplementation appreciably regained the body weight and heart weight of the investigational animals. Hemodynamic parameters and antioxidants statuses were escalated by the plumbagin treatment. The severe elevation in the cardiac damage markers and inflammatory markers were noticeably ameliorated by the plumbagin treatment. The plumbagin treatment also assuaged the overexpression of inflammatory and apoptotic proteins in the heart tissues of doxorubicin‐challenged rats. The histopathological analysis revealed that the plumbagin appreciably protected the heart tissues from the doxorubicin‐induced damages. The findings of this exploration evidenced that plumbagin treatment attenuated the doxorubicin‐stimulated cardiotoxicity in rats.

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Section: Methodsmentioning

confidence: 99%

Plumbagin protects the myocardial damage by modulating the cardiac biomarkers, antioxidants, and apoptosis signaling in the doxorubicin‐induced cardiotoxicity in rats

Chinnathambi

Alharbi

et al. 2020

Environmental Toxicology

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“…Moreover, the same research group recently obtained interesting data also on edaravone antioxidant capacities in the BDL rat model of obstructive cholestasis [201]. Edaravone showed potent antioxidant and radical scavenging activities in various pathologies, such as cerebral ischemia, stroke and amyotrophic lateral sclerosis [202][203][204], also improving oxidative stress-induced mitochondrial impairment in various diseases [205,206]. In their work, Ommati et al demonstrated that BDL-rats treated with edaravone, at a dose of 1-10 mg/kg/day intraperitoneally for 14 days, show significant improvements in cholestasis-associated hepatic and renal injury, via reduction of ROS levels, lipid peroxidation, protein carbonylation, and GSSG levels.…”

Section: Antioxidant Approach For the Treatment Of Cholestasismentioning

confidence: 96%

Changes in Glutathione Content in Liver Diseases: An Update

et al. 2021

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Glutathione (GSH), a tripeptide particularly concentrated in the liver, is the most important thiol reducing agent involved in the modulation of redox processes. It has also been demonstrated that GSH cannot be considered only as a mere free radical scavenger but that it takes part in the network governing the choice between survival, necrosis and apoptosis as well as in altering the function of signal transduction and transcription factor molecules. The purpose of the present review is to provide an overview on the molecular biology of the GSH system; therefore, GSH synthesis, metabolism and regulation will be reviewed. The multiple GSH functions will be described, as well as the importance of GSH compartmentalization into distinct subcellular pools and inter-organ transfer. Furthermore, we will highlight the close relationship existing between GSH content and the pathogenesis of liver disease, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic cholestatic injury, ischemia/reperfusion damage, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatocellular carcinoma. Finally, the potential therapeutic benefits of GSH and GSH-related medications, will be described for each liver disorder taken into account.

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“…and doxorubicin-induced cardiotoxicity. 44 In these studies, the cardioprotective effects of AV and ED were attributed mainly to their ability to attenuate oxidative stress. Therefore, we investigated the effect of AV and ED on LPO and the antioxidants GSH and SOD in the heart of CP-intoxicated rats.…”

mentioning

confidence: 99%

“…The ability of AV and ED to attenuate oxidative stress in different models of cardiac injury has been previously reported. 20,[40][41][42][43][44] In cisplatin-intoxicated rats, oral supplementation of 600 mg/L AV for 5 days decreased cardiac LPO and increased GSH. 40 AV increased cardiac GSH in isoproterenol-induced rats 41 and serum SOD and catalase in diabetic rats.…”

mentioning

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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Edaravone and benidipine protect myocardial damage by regulating mitochondrial stress, apoptosis signalling and cardiac biomarkers against doxorubicin-induced cardiotoxicity

Cited by 20 publications

References 43 publications

Plumbagin protects the myocardial damage by modulating the cardiac biomarkers, antioxidants, and apoptosis signaling in the doxorubicin‐induced cardiotoxicity in rats

Plumbagin protects the myocardial damage by modulating the cardiac biomarkers, antioxidants, and apoptosis signaling in the doxorubicin‐induced cardiotoxicity in rats

Changes in Glutathione Content in Liver Diseases: An Update

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

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