Cardioprotective and cardiotoxic effects of Quercetin and two of its in vivo metabolites on differentiated H9c2 cardiomyocytes

Daubney, J, Bonner, PL ORCID: https://orcid.org/0000-0001-9015-3403, Hargreaves, AJ ORCID: https://orcid.org/0000-0001-9754-5477 and Dickenson, JM ORCID: https://orcid.org/0000-0002-9683-969X, 2015. Cardioprotective and cardiotoxic effects of Quercetin and two of its in vivo metabolites on differentiated H9c2 cardiomyocytes. Basic & Clinical Pharmacology & Toxicology, 116 (2), pp. 96-109. ISSN 1742-7835

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Abstract

Whilst mitotic rat embryonic cardiomyoblast-derived H9c2 cells have been widely used as a model system to study the protective mechanisms associated with flavonoids, they are not fully differentiated cardiac cells. Hence the aim of this study was to investigate the cardioprotective and cardiotoxic actions of quercetin and two of its major in vivo metabolites, quercetin 3-glucuronide and 3’-O-methyl quercetin, using differentiated H9c2 cells. The differentiated cardiomyocyte-like phenotype was confirmed by monitoring expression of cardiac troponin 1 following 7 days of culture in reduced serum medium containing 10 nM all-trans retinoic acid. Quercetin-induced cardiotoxicity was assessed by monitoring MTT reduction, LDH release, caspase 3 activity and reactive oxygen species production following prolonged flavonoid exposure (72 h). Cardiotoxicity was observed with quercetin and 3’-O-methyl quercetin but not quercetin 3-glucuronide. Cardioprotection was assessed by pre-treating differentiated H9c2 cells with quercetin or its metabolites for 24 h prior to 2 h exposure to 600 µM H2O2, after which oxidative stress-induced cell damage was assessed by measuring MTT reduction and LDH release. Cardioprotection was observed with quercetin and 3’-O-methyl quercetin but not with quercetin 3-glucuronide. Quercetin attenuated H2O2-induced activation of ERK1/2, PKB, p38 MAPK and JNK but inhibitors of these kinases did not modulate quercetin-induced protection or H2O2-induced cell death. In summary, quercetin triggers cardioprotection against oxidative stress–induced cell death and cardiotoxicity following prolonged exposure. Further studies are required to investigate the complex interplay between the numerous signalling pathways that are modulated by quercetin and which may contribute to the cardioprotective and cardiotoxic effects of this important flavonoid.

Item Type:	Journal article
Publication Title:	Basic & Clinical Pharmacology & Toxicology
Creators:	Daubney, J., Bonner, P.L., Hargreaves, A.J. and Dickenson, J.M.
Publisher:	Wiley
Date:	February 2015
Volume:	116
Number:	2
ISSN:	1742-7835
Identifiers:	Number Type 10.1111/bcpt.12319 DOI
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	09 May 2016 10:46
Last Modified:	13 Oct 2017 12:05
URI:	https://irep.ntu.ac.uk/id/eprint/27748

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