دورية أكاديمية
d-Limonene complexed with cyclodextrin attenuates cardiac arrhythmias in an experimental model of doxorubicin-induced cardiotoxicity: Possible involvement of calcium/calmodulin-dependent protein kinase type II.
| العنوان: | d-Limonene complexed with cyclodextrin attenuates cardiac arrhythmias in an experimental model of doxorubicin-induced cardiotoxicity: Possible involvement of calcium/calmodulin-dependent protein kinase type II. |
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| المؤلفون: | Durço AO; Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil., Souza DS; Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil., Rhana P; Department of Physiology and Membrane Biology, University of California, Davis, USA., Costa AD; Department of Physiology and Membrane Biology, University of California, Davis, USA., Marques LP; Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil., Santos LABO; Department of Biology, Federal University of Sergipe, São Cristóvão, Brazil., de Souza Araujo AA; Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil; Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Brazil., de Aragão Batista MV; Department of Biology, Federal University of Sergipe, São Cristóvão, Brazil., Roman-Campos D; Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil., Santos MRVD; Health Science Graduate Program, Federal University of Sergipe, Aracaju, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil. Electronic address: marciorvsantos@academico.ufs.br. |
| المصدر: | Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2023 Sep 01; Vol. 474, pp. 116609. Date of Electronic Publication: 2023 Jun 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0333 (Electronic) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: New York. |
| مواضيع طبية MeSH: | Calcium*/metabolism , Cyclodextrins*, Mice ; Animals ; Limonene/adverse effects ; Limonene/metabolism ; Cardiotoxicity/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Molecular Docking Simulation ; Doxorubicin/adverse effects ; Arrhythmias, Cardiac/chemically induced ; Arrhythmias, Cardiac/prevention & control ; Arrhythmias, Cardiac/metabolism ; Myocytes, Cardiac |
| مستخلص: | Background: Arrhythmias are one manifestation of the cardiotoxicity that results from doxorubicin (Doxo) administration. Although cardiotoxicity is an anticipated outcome in anticancer therapies, there is still a lack of treatment options available for its effective management. This study sought to evaluate the possible cardioprotective effect of complex d-limonene (DL) plus hydroxypropyl-β-cyclodextrin (HβDL) during treatment with Doxo, focusing on the arrhythmic feature. Methods: Cardiotoxicity was induced in Swiss mice with Doxo 20 mg/kg, with 10 mg/kg of HβDL being administered 30 min before the Doxo. Plasma CK-MB and LDH levels were analyzed. Cellular excitability and susceptibility to cardiac and cardiomyocyte arrhythmias were evaluated using in vivo (pharmacological cardiac stress) and in vitro (burst pacing) ECG protocols. Ca 2+ dynamics were also investigated. The expression of CaMKII and its activation by phosphorylation and oxidation were evaluated by western blot, and molecular docking was used to analyze the possible interaction between DL and CaMKII. Results: Electrocardiograms showed that administration of 10 mg/kg of HβDL prevented Doxo-induced widening of the QRS complex and QT interval. HβDL also prevented cardiomyocyte electrophysiological changes that trigger cellular arrhythmias, such as increases in action potential duration and variability; decreased the occurrence of delayed afterdepolarizations (DADs) and triggered activities (TAs), and reduced the incidence of arrhythmia in vivo. Ca 2+ waves and CaMKII overactivation caused by phosphorylation and oxidation were also decreased. In the in silico study, DL showed potential inhibitory interaction with CaMKII. Conclusion: Our results show that 10 mg/kg of βDL protects the heart against Doxo-induced cardiotoxicity arrhythmias, and that this is probably due to its inhibitory effect on CaMKII hyperactivation. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Arrhythmia; CaMKII; Cardiotoxicity; Cyclodextrin; Doxorubicin; d-Limonene |
| المشرفين على المادة: | 9MC3I34447 (Limonene) SY7Q814VUP (Calcium) EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) 0 (Cyclodextrins) 80168379AG (Doxorubicin) |
| تواريخ الأحداث: | Date Created: 20230701 Date Completed: 20230807 Latest Revision: 20230808 |
| رمز التحديث: | 20230809 |
| DOI: | 10.1016/j.taap.2023.116609 |
| PMID: | 37392997 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0333 |
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| DOI: | 10.1016/j.taap.2023.116609 |