Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1
| Autor: | Fábio Henrique Fernandes, Leonardo da Cunha Menezes Souza, Daisy Maria Favero Salvadori, Paula Torres Presti, Ana Lúcia dos Anjos Ferreira |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Heart Diseases macromolecular substances Cardioprotection Pharmacology Fatty Acid-Binding Proteins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Coenzyme A Ligases polycyclic compounds Animals Medicine Fatty acid binding protein Myocytes Cardiac Doxorubicin Benzodioxoles Rats Wistar ALDH2 Cardiotoxicity Fatty acid metabolism medicine.diagnostic_test Triglyceride business.industry Aldehyde Dehydrogenase Mitochondrial Gene Expression Profiling organic chemicals ALDH2 activator technology industry and agriculture Lipid metabolism Lipid Metabolism Lipids carbohydrates (lipids) Disease Models Animal 030104 developmental biology chemistry Benzamides Energy Metabolism Transcriptome business Lipid profile 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| Popis: | Made available in DSpace on 2021-06-25T12:41:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-05 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) National Council for Scientific and Technological Development 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. Sao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Botucatu, SP, Brazil Sao Paulo State Univ, Med Sch, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Botucatu, SP, Brazil Sao Paulo State Univ, Med Sch, Botucatu, SP, Brazil FAPESP: FAPESP 2012/17280 FAPESP: 2014/09740-0 National Council for Scientific and Technological Development: CNPq 303435/2016 |
| Databáze: | OpenAIRE |
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