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

Abstract

BackgroundEntacapone (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/MethodsThe 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.ResultsENT (10 and 20 μM) 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.ConclusionsENT 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.

Evaluation of Vitamin C Supplementation on Kidney Function and Vascular Reactivity Following Renal Ischemic Injury in Mice

“…The possible explanation is that vitamin C may preserve GSH level via scavenging superoxide effectively. The free radical O 2 -at high level will react with NO to produce peroxynitrite [27]. There is a possibility that vitamin C restores NO level by reducing O 2 -.…”

“…Thus, vitamin C might protect renal vascular function via reducing ROS level and further improve kidney function in IRI. It should be noted that except for ROS, reactive nitrogen species (RNS) such as peroxynitrite also markedly aggravates oxidative stress injury [27]. Excessive peroxynitrite which is generated by the reaction between NO and elevated O 2 -could be critically instrumental in the vasoconstriction [46].…”

“…Vitamin C could react rapidly with O 2 -to play an antioxidant role in cytosol and extracellular matrix. It has been reported that vitamin C also scavenges peroxynitrite very effectively to prevent the formations of nitrotyrosine, nitrotryphophan and nitrated lipids [27]. In addition, intra-arterial administration of high dose of vitamin C results in improved vasodilation in hypertensive patients [28].…”

In vitro antioxidant and immunomodulatory activity of transglutaminase-treated sodium caseinate hydrolysates

“…For instance, atherosclerotic cardiovascular disease is characterised by the oxidation of lowdensity lipoproteins (LDL) which induce the adhesion and influx of monocytes and lead to cytokine production, a pro-inflammatory response (Singh, Devaraj, & Jialal, 2005). Some multifactorial diseases such as atherosclerosis or Parkinson's disease are the result of combined inflammatory and oxidative processes (Chen, Lü, Yao, & Chen, 2016). For this reason, there is an increasing interest in studies on the anti-inflammatory and antioxidant potential of bioactive dietary ingredients.…”

Comparative effects of Alpha Tocopherol and Ascorbic Acid on Chronic Stress Induced Neuropeptide Y Derangements

“…It prevents lipid peroxidation of membranes by interfering with the proliferation of lipid radicals and is capable of scavenging ROS. 6 Ascorbic acid (AA) or vitamin C is a hydrophilic compound, present in cytosol and extracellular fluid, either in reduced or oxidized forms, has the ability to act as a reducing agent or detoxifies various oxygen radicals in vivo. The antioxidant activity involves its conversion to oxidized form (dehydro-ascorbic acid) by donating two electrons to ROS, and helps in recycling tocopherol.…”