Quercetin protects cardiomyoblasts against hypertonic cytotoxicity by abolishing intracellular CaSUP2+/SUP elevations and mitochondrial depolarisation

0585591 - MBÚ 2025 RIV GB eng J - Journal Article
Dostál, Z. - Zholobenko, A. V. - Přichystalová, H. - Gottschalk, B. - Valentová, Kateřina - Malli, R. - Modrianský, M.
Quercetin protects cardiomyoblasts against hypertonic cytotoxicity by abolishing intracellular CaSUP2+/SUP elevations and mitochondrial depolarisation.
Biochemical Pharmacology. Roč. 222, April 2024 (2024), č. článku 116094. ISSN 0006-2952. E-ISSN 1873-2968
R&D Projects: GA ČR(CZ) GA23-04654S
Institutional support: RVO:61388971
Keywords : calcium * 2,3-dehydrosilybin * polyphenols * flavonoids * silymarin * apoptosis * injury * Hypertonic stress * Quercetin * 2,3-dehydrosilybin * H9c2 cells * Calcium
OECD category: Pharmacology and pharmacy
Impact factor: 5.8, year: 2022
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0006295224000777?via%3Dihub

Background and Aim: Osmotic changes represent a burden for the body and their limitation would be beneficial. We hypothesized that ubiquitous natural compounds could guard against cytotoxic effects of osmotic stress. We evaluated the anti-hypertonic mechanism of quercetin and 2,3-dehydrosilybin in H9c2 cells in vitro. Experimental procedure: Protective effect of both compounds was determined by neutral red assay, cell apoptosis was estimated by measuring caspase-3 activity and verified by western blot and annexin V assay. Phosphorylation level of selected proteins was also detected. Mitochondrial membrane potential was evaluated using dye JC-1. Ca2+ signals were evaluated using genetically encoded fluorescent Ca2+ biosensor GCaMP7f. Formation of reactive oxygen species was measured using an oxidant-sensing probe dihydrofluorescein diacetate. Key results: Quercetin protected H9c2 cells against hypertonic stress-induced cell death. We observed a significant increase in intracellular Ca2+ levels ([Ca2+]cyto) when cells originally placed in a hypertonic solution were returned to a normotonic environment. Quercetin was found to prevent this increase in [Ca2+]cyto and also the depolarization of mitochondrial membrane potential. Conclusions and implications: Quercetin, but not 2,3-dehydrosilybin, reduced adverse effects of osmotic stress mainly by dampening the elevation of [Ca2+]cyto and mitochondrial Ca2+ overload. This may consequently prevent MPTP pore opening and activation of apoptosis.
Permanent Link: https://hdl.handle.net/11104/0353287