Acute Cardioprotective and Cardiotoxic Effects of Bilberry Anthocyanins in Ischemia–Reperfusion Injury: Beyond Concentration-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.

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We thank the reviewers for their suggestions that improved this paper. We are grateful for the financial support by the Slovenian Research Agency [research projects J3-0024 and Z4-2280]; grant for international mobility of students (Ad Futura, Slovenia); Università di Trieste (Italy); Fondazione Cassa di Risparmio di Trieste and Ministero degli Affari Esteri (Cooperazione scientifica e tecnologica Italia-Slovenia 2006-2009).

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Correspondence to Lovro Ziberna.

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Ziberna, L., Lunder, M., Moze, S. et al. Acute Cardioprotective and Cardiotoxic Effects of Bilberry Anthocyanins in Ischemia–Reperfusion Injury: Beyond Concentration-Dependent Antioxidant Activity. Cardiovasc Toxicol 10, 283–294 (2010).

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  • Bilberry anthocyanins
  • Cellular antioxidant activity
  • Endothelium
  • Ischemia–reperfusion injury
  • Isolated rat heart