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

<p><b>Objectives</b>: Rutin, quercetin-3-<i>O</i>-rutinoside, a natural flavonol glycoside, has shown various <i>in vitro</i> 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.</p> <p><b>Methods</b>: 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.</p> <p><b>Results</b>: 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 <i>in vitro</i> and had the tendency to increase it <i>in vivo</i>.</p> <p><b>Conclusions</b>: Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used.</p>