Manitoba Lingonberry (Vaccinium vitis-idaea) Bioactivities in Ischemia-Reperfusion Injury

Lingonberry (Vaccinium vitis-idaea) harvested in Manitoba, Canada contains very high levels of anthocyanins and other polyphenols. These compounds are bioavailable in the kidney and, since other antioxidant compounds have been shown to protect against ischemia-reperfusion (IR) injury in various models, we hypothesized that the anthocyanins and polyphenols in Manitoba lingonberry would be bioactive against IR injury. Due to the significance of cardiomyocyte IR injury in cardiovascular disease and the prevalence of renal IR injury following major surgeries and kidney transplants, we selected three IR models to test for protective effects of Manitoba lingonberry against these types of injuries: simulated IR in H9c2 cardiomyoblasts, acute kidney injury (AKI) in Sprague-Dawley rats, and simulated IR in HK-2 kidney proximal tubule epithelial cells. First, the study showed the strong antioxidant capacity of Manitoba lingonberry and determined the major anthocyanins present. Second, the results showed that Manitoba lingonberry prevented apoptosis in H9c2 cells caused by IR injury or hydrogen peroxide-induced oxidative stress by inhibiting chromatin condensation, caspase activation, and MAPK signaling. Third, the study showed that rats who consumed lingonberry juice daily for three weeks had improved kidney function, reduced renal MAPK signaling, and an attenuated inflammatory response following AKI. Fourth, the link between renal MAPK signaling and inflammatory response was confirmed in HK-2 cells and pure lingonberry anthocyanins were shown to be effective at modulating this response. ii These results provide the first characterization of Manitoba lingonberry and highlight the importance of dietary berry compounds for cardiovascular and renal health. This study is the first to demonstrate the use of Manitoba lingonberry juice as a functional food and the first to demonstrate that physiological nanomolar doses of anthocyanins can protect heart and kidney cells from apoptosis.