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

Abstract

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.

Anthocyanins from Eugenia brasiliensis edible fruits as potential therapeutics for COPD treatment

“…Recently, increased attention has been given to the possible health benefits of these compounds in preventing chronic and degenerative diseases incluiding heart disease and cancer (Lim et al, 2011; Ziberna et al, 2010). The great abundance of this fruit in the southeast Brazil could make its fruits a promising anthocyanin-rich crop.…”

Toxicological aspects of the use of phenolic compounds in disease prevention

“…However, in recent years, both antioxidant and pro-oxidant activities were reported, depending upon certain experimental conditions (Halliwell, 2008; Ziberna et al , 2010). Often these pro-oxidant effects involve interactions of phenolic compounds with transition metal ions, which can be ubiquitously found in biologic systems, or as universal contaminants of biologic reagents (Halliwell, 2009).…”

“…A large number of studies have identified cellular targets that could be involved in the health promoting actions of dietary plant phenolic compounds. Epidemiological evidence indicates that diets rich in fruits and vegetables promote health and attenuate or delay the onset of many diseases (Knekt et al , 2002; Ghosh & Konishi, 2007; Rhone & Basu, 2008; Patil et al , 2009; Agte & Tarwadi, 2010; Cvorovic et al , 2010; Crozier et al , 2010; Ziberna et al , 2010; Kalt et al , 2010). The beneficial effects of fruits and vegetables have been largely ascribed to phenolic compounds, since ingestion of foods rich in these substances has been associated in humans and experimental animals with reduction in: i) dyslipidemia and atherosclerosis; ii) endothelial dysfunction and hypertension; iii) platelet activation and thrombosis; iv) inflammatory processes associated with induction and perpetuation of cardiovascular diseases (Fraga et al , 2010).…”

The Neuroprotective Potential of Cyanidin-3-glucoside Fraction Extracted from Mulberry Following Oxygen-glucose Deprivation

“…To our knowledge, however, no reports have demonstrated adverse effects of C3G. However, one study by Ziberna et al (2010) reported cardiotoxic effects of relatively high concentrations of anthocyanins extracted from bilberry fruit [43]. It was shown that at concentrations of 0.1~5µg/ml, anthocyanins extracted from bilberries conferred cardioprotective effects against ischemia-reperfusion injury in isolated rat hearts.…”