Quercetin and Its Derivative Counteract Palmitate-Dependent Lipotoxicity by Inhibiting Oxidative Stress and Inflammation in Cardiomyocytes

Author:

Granieri Maria Concetta1,Rocca Carmine1ORCID,De Bartolo Anna1,Nettore Immacolata Cristina2,Rago Vittoria3ORCID,Romeo Naomi1,Ceramella Jessica3ORCID,Mariconda Annaluisa4ORCID,Macchia Paolo Emidio2ORCID,Ungaro Paola5,Sinicropi Maria Stefania3ORCID,Angelone Tommaso16ORCID

Affiliation:

1. Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy

2. Dipartimento di Medicina Clinica e Chirurgia, Scuola di Medicina, Università degli Studi di Napoli Federico II, 80131 Naples, Italy

3. Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy

4. Department of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, Italy

5. Istituto per l’Endocrinologia e l’Oncologia Sperimentale (IEOS) “Gaetano Salvatore”, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy

6. National Institute of Cardiovascular Research (INRC), 40126 Bologna, Italy

Abstract

Cardiac lipotoxicity plays an important role in the pathogenesis of obesity-related cardiovascular disease. The flavonoid quercetin (QUE), a nutraceutical compound that is abundant in the “Mediterranean diet”, has been shown to be a potential therapeutic agent in cardiac and metabolic diseases. Here, we investigated the beneficial role of QUE and its derivative Q2, which demonstrates improved bioavailability and chemical stability, in cardiac lipotoxicity. To this end, H9c2 cardiomyocytes were pre-treated with QUE or Q2 and then exposed to palmitate (PA) to recapitulate the cardiac lipotoxicity occurring in obesity. Our results showed that both QUE and Q2 significantly attenuated PA-dependent cell death, although QUE was effective at a lower concentration (50 nM) when compared with Q2 (250 nM). QUE decreased the release of lactate dehydrogenase (LDH), an important indicator of cytotoxicity, and the accumulation of intracellular lipid droplets triggered by PA. On the other hand, QUE protected cardiomyocytes from PA-induced oxidative stress by counteracting the formation of malondialdehyde (MDA) and protein carbonyl groups (which are indicators of lipid peroxidation and protein oxidation, respectively) and intracellular ROS generation, and by improving the enzymatic activities of catalase and superoxide dismutase (SOD). Pre-treatment with QUE also significantly attenuated the inflammatory response induced by PA by reducing the release of key proinflammatory cytokines (IL-1β and TNF-α). Similar to QUE, Q2 (250 nM) also significantly counteracted the PA-provoked increase in intracellular lipid droplets, LDH, and MDA, improving SOD activity and decreasing the release of IL-1β and TNF-α. These results suggest that QUE and Q2 could be considered potential therapeutics for the treatment of the cardiac lipotoxicity that occurs in obesity and metabolic diseases.

Funder

University of Calabria

Publisher

MDPI AG

Subject

Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health

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