Acute Cardioprotective and Cardiotoxic Effects of BilberryAnthocyanins in Ischemia–Reperfusion Injury: BeyondConcentration-Dependent Antioxidant Activity

Despite being reported to reduce the risk of cardiovascular diseases, little is known about acute direct effects of bilberry anthocyanins on whole mammalian heart under ischemia-reperfusion (I-R) conditions. Bilberry anthocyanins were prepared from the ripe bilberries and analyzed using HPLC-DAD. Their antioxidant activity was evaluated by measuring the intrinsic free radical-scavenging capacity and by cellular antioxidant assay (CAA) on endothelial cells, where we quantified the intracellular capacity to inhibit the formation of peroxyl radicals. Experiments on the isolated rat hearts under I-R were carried out according to the Langendorff method. Perfusion with low concentrations of bilberry anthocyanins (0.01-1 mg/L) significantly attenuated the extent of I-R injury as evidenced by decreasing the release rate of LDH, increasing the postischemic coronary flow, and by decreasing the incidence and duration of reperfusion arrhythmias. High concentrations (5-50 mg/L) diminished cardioprotection and show cardiotoxic activity despite having their radical scavenging and intracellular antioxidant capabilities increased in a concentration-dependent manner. This study reveals the biphasic concentration-dependent bioactivity of bilberry anthocyanins under I-R, which results in strong cardioprotective activity in low concentrations and cardiotoxic activity in high concentrations.