Resveratrol Modulates miR-34a in Cardiotoxicity Induced by Isoproterenol

Boshra, Sylvia A.

doi:10.1089/jmf.2019.0209

Cited by 17 publications

(10 citation statements)

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“…Plant-derived polyphenols in this study significantly decreased cytokine protein confirming its anti-inflammatory activity that was previously reported [ 55 ]. Phenolic compounds were reported to decrease cytokine expression in different tissues and target miRNAs [ 56 , 57 , 58 , 59 ].…”

Section: Resultsmentioning

confidence: 99%

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies

et al. 2021

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In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (1–4) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC50) and SARS-CoV-2 inhibitory concentrations (IC50). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2, gallic acid 3, and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC50 values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.

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Section: Resultsmentioning

confidence: 99%

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies

et al. 2021

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“…When cardiomyocytes are injured, intracellular enzymes are released into the blood, therefore, these enzymes serve as markers for myocardial injury (37,38). Numerous studies (39)(40)(41) have shown that DOX treatment leads to increased serum CK and LDH levels.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of biomarkers for doxorubicin‑induced cardiac injury in rats

Pan

Wan

2022

Exp Ther Med

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Drug-induced cardiotoxicity is a leading cause of failure in drug development and predicting its occurrence in non-clinical studies is the primary preventive measure. The present study aimed to evaluate the changes in biomarkers during acute and chronic myocardial injury induced by doxorubicin (DOX) in rats. A rat model of acute myocardial injury was established through a single-dose, intraperitoneal injection of DOX (40 mg/kg), the changes in biomarkers were measured at 2, 4, 8 and 24 h after administration, following DOX administration, creatine kinase (CK) and fatty acid-binding protein 3 (FABP3) levels increased between 8 and 24 h, whereas cardiac troponin I (cTnI) peaked at 8 h. To establish a chronic myocardial injury model, rats received 1, 2 or 3 mg/kg DOX weekly by caudal vein injection for 2, 4, 6 or 7 weeks, the changes in biomarkers were detected at 2, 4, 6 and 8 weeks, the results showed that cTnI increased significantly after 2 and 8 weeks of administration. A significant increase in FABP3 and microRNA (miR)-146b levels was observed after 8 weeks of administration. Receiver operating characteristic curve and correlation analysis showed that cTnI and miR-146b had relatively high predictive values for chronic myocardial injury (area under the curve, 0.83 and 0.71, respectively) and were closely correlated with myocardial damage. These data suggested that CK, cTnI and FABP3 were relatively sensitive to DOX-induced acute myocardial injury, whereas cTnI and miR-146b were relatively sensitive to DOX-induced chronic myocardial injury.

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“…Clinical studies have reported increased miR-34a expression in plasma after acute myocardial infarction (Matsumoto et al, 2013) and in hearts following dilated cardiomyopathy (Boon et al, 2013). Elevated expression of miR-34a has also been noted in rodent hearts following induced myocardial infarction (Boon et al, 2013;Boshra, 2020;Elzenaar et al, 2013) and in the myocardial infarction border zone in mice (Boon et al, 2013), suggesting miR-34a involvement during cardiac damage. Boon et al (2013) also demonstrated reduced apoptosis and fibrosis and improved cardiac function following inhibition of miR-34a by treatment of mice with Anti-34a.…”

Section: Significance Of Mir-34a In the Heartmentioning

confidence: 98%

MicroRNA‐34a‐5p as a promising early circulating preclinical biomarker of doxorubicin‐induced chronic cardiotoxicity

Desai

Vijay

Lee

et al. 2022

J of Applied Toxicology

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Cardiotoxicity is a serious adverse effect of an anticancer drug, doxorubicin (DOX), which can occur within a year or decades after completion of therapy. The present study was designed to address a knowledge gap concerning a lack of circulating biomarkers capable of predicting the risk of cardiotoxicity induced by DOX. Profiling of 2083 microRNAs (miRNAs) in mouse plasma revealed 81 differentially expressed miRNAs 1 week after 6, 9, 12, 18, or 24 mg/kg total cumulative DOX doses (earlyonset model) or saline (SAL). Among these, the expression of seven miRNAs was altered prior to the onset of myocardial injury at 12 mg/kg and higher cumulative doses. The expression of only miR-34a-5p was significantly (false discovery rate [FDR] < 0.1) elevated at all total cumulative doses compared with concurrent SALtreated controls and showed a statistically significant dose-related response. The trend in plasma miR-34a-5p expression levels during DOX exposures also correlated with a significant dose-related increase in cardiac expression of miR-34a-5p in these mice. Administration of a cardioprotective drug, dexrazoxane, to mice before DOX treatment, significantly mitigated miR-34a-5p expression in both plasma and heart in conjunction with attenuation of cardiac pathology. This association between plasma and heart may suggest miR-34a-5p as a potential early circulating marker of earlyonset DOX cardiotoxicity. In addition, higher expression of miR-34a-5p (FDR < 0.1) in plasma and heart compared with SAL-treated controls 24 weeks after 24 mg/kg total cumulative DOX dose, when cardiac function was altered in our recently established delayed-onset cardiotoxicity model, indicated its potential as an early biomarker of delayed-onset cardiotoxicity.

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Resveratrol Modulates miR-34a in Cardiotoxicity Induced by Isoproterenol

Cited by 17 publications

References 50 publications

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies

Evaluation of biomarkers for doxorubicin‑induced cardiac injury in rats

MicroRNA‐34a‐5p as a promising early circulating preclinical biomarker of doxorubicin‐induced chronic cardiotoxicity

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