title: Intravenous rutin in rat exacerbates isoprenaline-induced cardiotoxicity likely due to intracellular oxidative stress.
abstract: OBJECTIVE
  Rutin, quercetin-3-O-rutinoside, a natural flavonol glycoside, has shown various in vitro benefits with potential use treating human diseases, especially cardiovascular system disorders. Antioxidant properties are assumed to underlie the majority of these benefits. Yet rutin pro-oxidant properties have been reported as well. Our research group has recently shown aggravating effects on isoprenaline (ISO)-induced cardiotoxicity in Wistar:Han rats after 24 hours.
  
  
  METHODS
  This study was designed to examine in more detail the reasons for the negative effects of rutin (11.5 and 46 mg/kg, i.v.) after administration of ISO (100 mg/kg, s.c.) in rats within 2 hours of continuous experiment and in the H9c2 cardiomyoblast-derived cell line.
  
  
  RESULTS
  Like our previous findings, rutin did not (11.5 or 46 mg/kg, i.v.) reduce the ISO-induced mortality within 2 hours although the lower dose significantly reduced cardiac troponin T (cTnT) and partly improved the histological findings. In contrast, the higher dose increased the mortality in comparison with solvent (1.26% w/v sodium bicarbonate). This was not caused by any specific haemodynamic disturbances. It appears to be associated with oxidative stress as rutin enhanced intracellular reactive oxygen species formation in vitro and had the tendency to increase it in vivo.
  
  
  CONCLUSIONS
  Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Filipský
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Říha
authors.affiliation: b Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Pavlína
authors.initials: P
authors.lastname: Hašková
authors.affiliation: c Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Pilařová
authors.affiliation: c Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Nováková
authors.affiliation: d Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Semecký
authors.affiliation: e Faculty of Medicine in Hradec Králové , Charles University in Prague , Šimkova 870, 500 38 Czech Republic.|f University Hospital Hradec Králové , Sokolská 581, 500 05 Czech Republic.
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Vávrová
authors.affiliation: e Faculty of Medicine in Hradec Králové , Charles University in Prague , Šimkova 870, 500 38 Czech Republic.|f University Hospital Hradec Králové , Sokolská 581, 500 05 Czech Republic.
authors.forename: Magdaléna
authors.initials: M
authors.lastname: Holečková
authors.affiliation: e Faculty of Medicine in Hradec Králové , Charles University in Prague , Šimkova 870, 500 38 Czech Republic.|f University Hospital Hradec Králové , Sokolská 581, 500 05 Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Palicka
authors.affiliation: b Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Šimůnek
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Radomír
authors.initials: R
authors.lastname: Hrdina
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
authors.forename: Přemysl
authors.initials: P
authors.lastname: Mladěnka
mesh_terms: D000818:Animals; D066126:Cardiotoxicity / Q000209:etiology* / Q000401:mortality; D002460:Cell Line; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005978:Glutathione / Q000097:blood; D006321:Heart / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D009206:Myocardium / Q000473:pathology; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D012431:Rutin; D015237:Dinoprost; D005978:Glutathione; D007545:Isoproterenol
keywords: Catecholamine; Flavonoid; H9c2 cell line; Isoprenaline; Reactive oxygen species; Rutin; Wistar rat