Entacapone is an Antioxidant More Potent than Vitamin C and Vitamin E for Scavenging of Hypochlorous Acid and Peroxynitrite, and the Inhibition of Oxidative Stress-Induced Cell Death

Background: Entacapone (ENT), a clinical drug for the treatment of Parkinson's disease, has been shown to have antioxidant effects, but little is known about its antioxidant mechanisms. The objective of the current study was to determine the antioxidant activity of ENT against different species of oxidants and compared it with that of vitamin C and vitamin E. We also determined the effect of ENT on oxidative stress-induced cell death in human umbilical vein endothelial cells (HUVECs). Material/Methods: The total antioxidant activities of ENT, vitamin C and vitamin E were determined with a standard DPPH-scavenging assay. Specific assays to determine ENT's scavenging activity on hypochlorous acid (HOCl), peroxynitrite (ONOO-), and hydrogen peroxide (H2O2), and the chelating effect on Fe(II) were used. H2O2-induced cell death in HUVECs was determined with the MTT assay. Results: ENT (10 and 20 mu M) scavenged 60% and 83% of DPPH activity, respectively. These percentages were greater than those resulting from using the same concentrations of vitamin C and vitamin E. ENT's HOCl-scavenging activity was concentration-dependent and 8 to 20 times stronger than those of vitamin C and vitamin E. ENT's ONOO--scavenging activity was 8% to 30% stronger than that of vitamin C. However, ENT, vitamin C, and vitamin E were not able to directly scavenge H2O2, and did not show any chelating effect on Fe(II). Importantly ENT, but not vitamin C or vitamin E, inhibited H2O2-induced cell death in HUVECs. Conclusions: ENT is an antioxidant that can scavenge toxic HOCl and ONOO-species and inhibit oxidative stress-induced cell death more effectively than vitamin C and vitamin E. ENT may have new clinical applications as an antioxidant in the treatment of ROS-induced diseases including cardiovascular disease, cancer, and neurodegenerative diseases.