Double-edged sword behaviour of gallic acid and its interaction with peroxidases in human microvascular endothelial cell culture (HMEC-1). Antioxidant and pro-oxidant effects.

  • José Serrano NUTREN Department of Experimental Medicine, University of Lleida-IRBLleida, Spain. <>;
  • Ana Cipak
  • Jordi Boada
  • Hugo Gonzalo
  • Daniel Cacabelos
  • Anna Cassanye
  • Reinald Pamplona
  • Neven Zarkovic
  • Manuel Portero-Otin


A previous report from our group had shown in vitro a direct interaction between peroxidases and dietary antioxidants at physiological concentrations, where in the absence of H(2)O(2), the antioxidants could serve as oxidizing substrates for the peroxidases. However, the physiological relevance of those findings had not been evaluated. The main objective of this study was to determine whether the oxidizing products produced in the interaction between peroxidase and gallic acid at a physiological concentration of 1 microM may promote cell death or survival in a human microvascular endothelial cell line (HMEC-1). Our findings suggested that gallic acid may show a double-edged sword behaviour, since in the absence of H(2)O(2) it may have a pro-oxidant effect which may promote cell injury (evidenced by LDH, Crystal Violet and calcein AM viability/citotoxicity assays), while in the presence of H(2)O(2), gallic acid may act as an antioxidant inhibiting oxidative species produced in the peroxidase cycle of peroxidases. These observations were confirmed with several oxidative stress biomarkers and the evaluation of the activation of cell survival pathways like AKT and MAPK/ERK.