Gas Plasma-Induced Oxidative Transformation of Glucose

<b>Background</b>: Glucose, a central carbohydrate in higher organisms' metabolism, can undergo extensive oxidative modification under conditions of excessive inflammation or elevated reactive oxygen and nitrogen species (RONS). Such modifications yield glucose oxidation products (GOPs) with potential biological relevance and toxicity. This study aimed to systematically characterize GOP formation under defined oxidative conditions generated by gas plasma treatment. <b>Methods</b>: <i>D</i>-glucose solutions were prepared at 0.25 mM (hypoglycemic/diabetic range), 2.5 mM (sub-physiological), and 25 mM (peritoneal dialysis fluid). Samples were exposed for up to 20 min to the atmospheric-pressure argon plasma jet kINPen, which produces a wide spectrum of RONS. Treatment time-dependent glucose oxidation was assessed by high-resolution mass spectrometry (HRMS) and tandem mass spectrometry (MS/MS) to identify the oxidation products. <b>Results</b>: Gas plasma exposure generated various oxidation products and their abundance profiles depended on initial glucose concentration and treatment duration. Identified products included 2-keto-<i>D</i>-glucose, 3-deoxyglucosone (3DG), 3,4-dideoxyglucosone-3-ene (3,4DGE), furaldehyde, methylglyoxal, and acetaldehyde. HRMS/MS analysis confirmed diagnostic fragment ions for each GOP and revealed distinct formation across the model scenarios. <b>Conclusions</b>: Cold gas plasma induces a spectrum of glucose oxidation products under biomedically relevant glucose levels. The identified GOPs, many of which have known cytotoxic or signaling properties, provide mechanistic insight into glucose oxidation in inflamed or oxidative microenvironments. These findings support the utility of plasma-based oxidative models for studying GOP-associated biological effects and potential pathophysiological consequences.