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Intravenous rutin in rat exacerbates isoprenaline-induced cardiotoxicity likely due to intracellular oxidative stress

T. Filipský, M. Říha, P. Hašková, V. Pilařová, L. Nováková, V. Semecký, J. Vávrová, M. Holečková, V. Palicka, T. Šimůnek, R. Hrdina, P. Mladěnka,

. 2017 ; 22 (2) : 78-90. [pub] 20160321

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc17024069

OBJECTIVES: 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.

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$a OBJECTIVES: Rutin, quercetin-3-O-rutinoside, a natural flavonol glycoside, has shown various in vitro benefits with potential use treating human diseases, especially cardiovascular system disorders. Antioxidant properties are assumed to underlie the majority of these benefits. Yet rutin pro-oxidant properties have been reported as well. Our research group has recently shown aggravating effects on isoprenaline (ISO)-induced cardiotoxicity in Wistar:Han rats after 24 hours. METHODS: This study was designed to examine in more detail the reasons for the negative effects of rutin (11.5 and 46 mg/kg, i.v.) after administration of ISO (100 mg/kg, s.c.) in rats within 2 hours of continuous experiment and in the H9c2 cardiomyoblast-derived cell line. RESULTS: Like our previous findings, rutin did not (11.5 or 46 mg/kg, i.v.) reduce the ISO-induced mortality within 2 hours although the lower dose significantly reduced cardiac troponin T (cTnT) and partly improved the histological findings. In contrast, the higher dose increased the mortality in comparison with solvent (1.26% w/v sodium bicarbonate). This was not caused by any specific haemodynamic disturbances. It appears to be associated with oxidative stress as rutin enhanced intracellular reactive oxygen species formation in vitro and had the tendency to increase it in vivo. CONCLUSIONS: Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used.
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$a Říha, Michal $u a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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$a Hašková, Pavlína $u b Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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$a Pilařová, Veronika $u c Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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$a Nováková, Lucie $u c Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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$a Semecký, Vladimír $u d Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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$a Vávrová, Jaroslava $u e Faculty of Medicine in Hradec Králové , Charles University in Prague , Šimkova 870, 500 38 Czech Republic. f University Hospital Hradec Králové , Sokolská 581, 500 05 Czech Republic.
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$a Holečková, Magdaléna $u e Faculty of Medicine in Hradec Králové , Charles University in Prague , Šimkova 870, 500 38 Czech Republic. f University Hospital Hradec Králové , Sokolská 581, 500 05 Czech Republic.
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$a Palicka, Vladimir $u e Faculty of Medicine in Hradec Králové , Charles University in Prague , Šimkova 870, 500 38 Czech Republic. f University Hospital Hradec Králové , Sokolská 581, 500 05 Czech Republic.
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$a Šimůnek, Tomáš $u b Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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$a Hrdina, Radomír $u a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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$a Mladěnka, Přemysl $u a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové , Charles University in Prague , Heyrovského 1203, 500 05 Czech Republic.
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