Concentration-Response Relationships of the Non-enzymatic Scavenging Activity of Ethyl Pyruvate Against Multiple Free Radicals

Background Pyruvate is a metabolic intermediate of energy metabolism that connects glycolysis and the tricarboxylic acid cycle. It also acts as an antioxidant, although it is unstable in solution. Ethyl pyruvate is a derivative of pyruvate with stability and lipid solubility and has been reported to have antioxidative activity. This study aimed to illustrate the concentration-response relationships of the non-enzymatic scavenging activity of ethyl pyruvate against multiple free radicals in vitro. Methodology Eight kinds of free radicals and singlet oxygen were generated in sample tubes. The direct scavenging activities of ethyl pyruvate against free radicals were evaluated by electron spin resonance spectroscopy using the spin-trapping method. Reaction rate constants were estimated from half-maximal inhibitory concentrations of concentration-response relationships. Results Ethyl pyruvate significantly scavenged the following six species of free radicals in concentration-dependent manners: hydroxyl radical (<i>k</i> _{ethyl pyruvate} = 1.4 × 10⁸ M^-1s^-1), superoxide anion (4.6 × 10³ M^-1s^-1), <i>tert</i>-butoxyl radical (0.91 × <i>k</i> _CYPMPO), ascorbyl free radical (0.77 × <i>k</i> _edaravone), singlet oxygen (0.19 × <i>k</i> _{4-OH_TEMP}), and nitric oxide (8.6 M^-1s^-1). However, ethyl pyruvate did not scavenge <i>tert</i>-butyl peroxyl radical, <i>tert</i>-butyl hydroperoxide, 2,2-diphenyl-1-picrylhydrazyl, and tyrosyl radical. Conclusions It is speculated that the protective activity of ethyl pyruvate against oxidative stress might be attributable to non-enzymatic free radical scavenging activity.