Abstract
Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. The flavonoid quercetin is a potent ROS scavenger, with several beneficial effects for the cardiovascular system, including antihypertrophic effects. Oxidative imbalance has been implicated in cardiac hypertrophy and heart failure. In this work, we tested whether quercetin could attenuate cardiac hypertrophy by improving redox balance and mitochondrial homeostasis. To test this hypothesis, we treated a group of mice with isoproterenol (30 mg/kg/day) for 4 or 8 consecutive days. Another group received quercetin (10 mg/kg/day) from day 5th of isoproterenol treatment. We carried out the following assays in cardiac tissue: measurement of cardiac hypertrophy, protein sulfhydryl, catalase, Cu/Zn and Mn-superoxide dismutase (SOD) activity, detection of H2O2, and opening of the mitochondrial permeability transition pore. The animals treated with isoproterenol for the initial 4 days showed increased cardiac weight/tibia length ratio, decreased protein sulfhydryl content, compromised SOD and catalase activity, and high H2O2 levels. Quercetin was able to attenuate cardiac hypertrophy, restore protein sulfhydryl, and antioxidant activity, in addition to efficiently blocking the H2O2. We also observed that isoproterenol decreases mitochondrial SOD activity, while quercetin reverses it. Strikingly, quercetin also protects mitochondria against the opening of mitochondrial permeability transition pore. Taken together, these results suggest that quercetin is capable of reversing established isoproterenol-induced cardiac hypertrophy through the restoration of cellular redox balance and protecting mitochondria.
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Acknowledgment
We acknowledge the technical assistance of Antônio F. R. Santos.
Funding
Amanda Albuquerque Cabral and Yuana Ivia Ponte Viana are recipients of research scholarships from UFCA. Joana Varlla de L. Alexandre is a scholarship holder from CAPES. This research was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP—grant number 88887.166577/2018-01), by the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq to Heberty Tarso Facundo (Grant number 409489/2018-2) and by UFCA (Edital ConsolidaPG). Alicia J. Kowaltowski is supported by the Centro de Pesquisa, Inovação e Difusão de Processos Redox em Biomedicina (FAPESP 13/07937-8) and CNPq.
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We declare that all authors meet the criteria for authorship according to ICMJE. JVLA, YIPV, ALNV, and HTF designed methods, performed the experiments, analyzed, and interpreted the results. JVLA, YIPV, CEBD, PLOC, ACA, and HTF co-designed and worked together mitochondrial and H2O2 experiments. AJK contributed to design the work, drafting the work, and revising it critically. All authors read and approved the final version of the manuscript. All data were generated in-house and no paper mill was used.
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de Lacerda Alexandre, J.V., Viana, Y.I.P., David, C.E.B. et al. Quercetin treatment increases H2O2 removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy. Naunyn-Schmiedeberg's Arch Pharmacol 394, 217–226 (2021). https://doi.org/10.1007/s00210-020-01953-8
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DOI: https://doi.org/10.1007/s00210-020-01953-8