Direct administration of rutin does not protect against catecholamine cardiotoxicity.
High levels of catecholamines are cardiotoxic and may trigger acute myocardial infarction (AMI). Similarly, the synthetic catecholamine isoprenaline (ISO) evokes a pathological state similar to AMI. During AMI there is a marked increase of free iron and copper which are crucial catalysts of reactive oxygen species formation. Rutin, a natural flavonoid glycoside possessing free radical scavenging and iron/copper chelating activity, may therefore be potentially useful in reduction of catecholamine cardiotoxicity as was previously demonstrated after its long-term peroral administration. Male Wistar:Han rats received rutin (46 or 11.5 mg kg(-1) i.v.) alone or with necrogenic dose of ISO (100 mg kg(-1) s.c.). Haemodynamic parameters were measured 24h after drug application together with analysis of blood, myocardial content of elements and histological examination. Results were confirmed by cytotoxicity studies using cardiomyoblast cell line H9c2. Rutin in a dose of 46 mg kg(-1) aggravated ISO-cardiotoxicity while the dose of 11 mg kg(-1) had no effect. These unexpected results were in agreement with in vitro experiments, where co-incubation with larger concentrations of rutin significantly augmented ISO cytotoxicity. Our results, in contrast to previous studies in the literature, suggest that the reported positive effects of peroral administration of rutin were unlikely to have been mediated by rutin per se but probably by its metabolite(s) or by some other, at this moment, unknown adaptive mechanism(s), which merit further investigation.
Mladenka
Premysl
P
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology, Czech Republic.
Zatloukalová
Libuse
L
Simůnek
Tomás
T
Bobrovová
Zuzana
Z
Semecký
Vladimír
V
Nachtigal
Petr
P
Hasková
Pavlína
P
Macková
Eliska
E
Vávrová
Jaroslava
J
Holecková
Magdaléna
M
Palicka
Vladimir
V
Hrdina
Radomír
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002614:Chelating Agents / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D006334:Heart Function Tests; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D002614:Chelating Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D012431:Rutin; D005978:Glutathione; D007545:Isoproterenol