دورية أكاديمية
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1.
| العنوان: | Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1. |
|---|---|
| المؤلفون: | da Cunha Menezes Souza L; Department of Pathology, Botucatu Medical School, São Paulo State University, Botucatu, São Paulo, Brazil. Electronic address: leonardo.menezes@unesp.br., Fernandes FH; Department of Pathology, Botucatu Medical School, São Paulo State University, Botucatu, São Paulo, Brazil., Presti PT; Medical School, São Paulo State University, Botucatu, Brazil., Anjos Ferreira AL; Medical School, São Paulo State University, Botucatu, Brazil., Fávero Salvadori DM; Department of Pathology, Botucatu Medical School, São Paulo State University, Botucatu, São Paulo, Brazil. |
| المصدر: | European journal of pharmacology [Eur J Pharmacol] 2021 May 05; Vol. 898, pp. 173955. Date of Electronic Publication: 2021 Feb 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : Amsterdam : Elsevier Science Original Publication: Amsterdam, North Holland Pub. Co. |
| مواضيع طبية MeSH: | Doxorubicin* , Transcriptome*, Benzamides/*pharmacology , Benzodioxoles/*pharmacology , Energy Metabolism/*drug effects , Heart Diseases/*prevention & control , Lipid Metabolism/*drug effects , Myocytes, Cardiac/*drug effects, Aldehyde Dehydrogenase, Mitochondrial/genetics ; Aldehyde Dehydrogenase, Mitochondrial/metabolism ; Animals ; Cardiotoxicity ; Coenzyme A Ligases/genetics ; Coenzyme A Ligases/metabolism ; Disease Models, Animal ; Energy Metabolism/genetics ; Fatty Acid-Binding Proteins/genetics ; Fatty Acid-Binding Proteins/metabolism ; Gene Expression Profiling ; Heart Diseases/chemically induced ; Heart Diseases/genetics ; Heart Diseases/metabolism ; Lipid Metabolism/genetics ; Lipids/blood ; Male ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Rats, Wistar ; Rats |
| مستخلص: | The use of doxorubicin (DOX) as an antineoplastic drug is compromised by its cardiotoxicity risk. Although several mechanisms have been proposed for DOX-induced cardiac dysfunction, there is still increased interest in assessing its effects. Likewise, it is important to find protocols that can prevent or minimize the side effects of DOX without hindering its antitumor activity. Thus, this study was designed to investigate the molecular mechanisms underlying DOX cardiotoxicity, with a special focus on cardiac energy metabolism and the ability of Alda-1 (ALDH2 agonist) to prevent DOX-induced cardiac alterations. We explored the effects of DOX on the histological morphology of the myocardium, on lipid profile, and on the expression of genes related to fatty acid metabolism, in the presence and absence of Alda-1 (8 mg/kg body weight; b.wt.). Two DOX treatment protocols were used: a single dose of DOX (4 mg/kg b.wt.); four doses of DOX (4 mg/kg b.wt.), one dose/week, for 4 weeks. Treatment with DOX caused a progressive injury in the cardiac tissue and an increase in the blood total cholesterol, high-density lipoproteins, very low-density lipoproteins and triglyceride, as well as an up-regulation of FABP4 (DOX and DOX + Alda-1 groups) and Slc27a2 (in DOX-treated animals). Alda-1 administration promoted reduction in the severity of the histopathological injuries (after single dose of DOX) and Slc27a2 overexpression was restored. In conclusion, the study revealed novel insights regarding the development of DOX-mediated cardiomyopathy, indicating a relationship between DOX exposure and FABP4 and Slc27a2 overexpression, and confirmed the cardioprotective effect of Alda-1. (Copyright © 2021 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ALDH2 activator; Cardioprotection; Cardiotoxicity; Fatty acid binding protein |
| المشرفين على المادة: | 0 (Benzamides) 0 (Benzodioxoles) 0 (FABP4 protein, rat) 0 (Fatty Acid-Binding Proteins) 0 (Lipids) 0 (N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide) 80168379AG (Doxorubicin) EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial) EC 1.2.1.3 (Aldh2 protein, rat) EC 6.2.1.- (Coenzyme A Ligases) EC 6.2.1.- (Slc27a2 protein, rat) |
| تواريخ الأحداث: | Date Created: 20210222 Date Completed: 20210519 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| DOI: | 10.1016/j.ejphar.2021.173955 |
| PMID: | 33617823 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0712 |
|---|---|
| DOI: | 10.1016/j.ejphar.2021.173955 |