Biochemical Pharmacology, 222, 116094: 1-12 (2024)

IF 5,8

Quercetin protects cardiomyoblasts against hypertonic cytotoxicity by abolishing intracellular Ca²⁺ elevations and mitochondrial depolarisation

Z. Dostál, A.V. Zholobenko, H. Přichystalová, B. Gottschalk, K. Valentová, R. Malli, M. Modrianský

 Abstract

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. 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. 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. 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.

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