RESUMEN
Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.