Oral administration of quercetin is unable to protect against isoproterenol cardiotoxicity
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Catecholamines are endogenous amines that participate in the maintenance of cardiovascular system homeostasis. However, excessive release or exogenous administration of catecholamines is cardiotoxic. The synthetic catecholamine, isoprenaline (isoproterenol, ISO), with non-selective β-agonistic activity has been used as a viable model of acute myocardial toxicity for many years. Since the pathophysiology of ISO–cardiotoxicity is complex, the aim of this study was to elucidate the effect of oral quercetin pretreatment on myocardial ISO toxicity. Wistar–Han rats were randomly divided into four groups: solvent or quercetin administered orally by gavage in a dose of 10 mg kg−1 daily for 7 days were followed by s.c. water for injection or ISO in a dose of 100 mg kg−1. Haemodynamic, ECG and biochemical parameters were measured; effects on blood vessels and myocardial histology were assessed, and accompanying pharmacokinetic analysis was performed. Quercetin was unable to protect the cardiovascular system against acute ISO cardiotoxicity (stroke volume decrease, cardiac troponin T release, QRS-T junction elevation and histological impairment). The sole positive effect of quercetin on catecholamine-induced cardiotoxicity was the normalization of increased left ventricular end-diastolic pressure caused by ISO. Quercetin did not reverse the increased responsiveness of rat aorta to vasoconstriction in ISO-treated animals, but it decreased the same parameter in the control animals. Accompanying pharmacokinetic analysis showed absorption of quercetin and its metabolite 3-hydroxyphenylacetic acid formed by bacterial microflora. In conclusion, a daily oral dose of 10 mg kg−1 of quercetin for 7 days did not ameliorate acute ISO–cardiovascular toxicity in rats despite minor positive cardiovascular effects.
KeywordsCardiotoxicity Catecholamine Isoproterenol Quercetin
This study was supported by a grant from the Czech Science Foundation project no. P303/12/G163. V.P., M.H. and J.V. thank MH CZ-DRO and the programme PRVOUK P37/11. M.Ř. would like to thank Charles University (GAUK 605712C and SVV 267 003). The authors wish to thank Mrs. Pavlína Lukešová, Mrs. Anežka Kunová and Miss Renata Exnarová for their excellent technical assistance and to Dr. Alexander Oulton for the language correction.
Conflict of interest
The authors declare that they have no conflict of interest.
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