Oral administration of quercetin is unable to protect against isoproterenol cardiotoxicity

Abstract

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.

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

“…Calpain activated pathway may lead to contractile malfunctioning of heart, cytoskeleton damage, and cell death (Vanderklish & Bahr, ). Being a flavonoid, the major concern in clinical translation is the oral bioavailability as one of the study showed that oral administration of quercetin could not protect against ISP‐induced toxicity (Ríha et al, ). However, these ubiquitously available phytoconstituents should be used in regular diet to reduce the risk of CVDs.…”

Curcumin ameliorated myocardial infarction by inhibition of cardiotoxicity in the rat model

“…In some cases, it was reported that a higher dose of flavonoids such as rutin not only increased MI histopathological changes but also exacerbated the intensity of MI-related injuries. 15 For this reason, we decided to return this area and analyze the therapeutic effect of cur on experimental infraction in a model of rat induced by a synthetic β-adrenoreceptor antagonist namely isoproterenol hydrochloride (ISO). It seems that the results of the current experiment could pave a way to detect the possible advantages and drawbacks of distinct medicinal compound notably cur in the field of cardiovascular disease notably MI.…”

“…In contrast, the promising effects of cur on cardiovascular disease, serious discrepancies, and opposite results have been previously shown in this area by numerous experiments. In some cases, it was reported that a higher dose of flavonoids such as rutin not only increased MI histopathological changes but also exacerbated the intensity of MI‐related injuries . For this reason, we decided to return this area and analyze the therapeutic effect of cur on experimental infraction in a model of rat induced by a synthetic β‐adrenoreceptor antagonist namely isoproterenol hydrochloride (ISO).…”

Comprehensive review of cardiovascular toxicity of drugs and related agents

“…Because of the complex pathophysiology, it is not surprising that no single agent can fully prevent/revert the injury caused by isoprenaline, or only works in low doses of isoprenaline . There are many reports showing that various natural compounds fully protect against isoprenaline cardiac injury in animal models, but it is not clear whether these studies have been performed according to the appropriate experimental standards …”

“…103,[109][110][111][112][113][114] There are many reports showing that various natural compounds fully protect against isoprenaline cardiac injury in animal models, 115,116 but it is not clear whether these studies have been performed according to the appropriate experimental standards. 117,118 2 -agonists, when inhaled at therapeutic doses to treat bronchoconstriction, are considered to be relatively safe from the cardiovascular point of view; however, their selectivity is not absolute and in higher doses they also bind to 1 -receptors. As a consequence, vasodilation due to 2 -receptor stimulation can be accompanied tachycardia due to either reflex sympathetic activation or nonselectivity.…”