CONICET | Buscador de Institutos y Recursos Humanos

Alloxan is apparently selectively taken up by the GLUT-2 glucose transporter in the pancreatic b-cell membrane [1, 2] causing diabetes in experimental animals. Nowadays, it is well established that, a redox cycling involving alloxan and its reduced product dialuric acid initiates an intracellular generation of reactive oxygen species, ROS, [3, 4, 5] mediated by physiological glutathione and other thiols. Despite the abundant literature on alloxan aqueous stability and the importance of alloxan-dialuric acid redox cycling in producing ROS capable of inducing diabetes mellitus in animals, there is still confusion on the reactions involved in these processes. Therefore, we describe here our investigations on the stability of alloxan aqueous solutions and on the molecular oxygen-mediated oxidation of dialuric acid to alloxan at physiologic pH with the aim of helping to understand the reaction mechanisms involved. To this purpose we have conducted time-resolved kinetic experiments on the oxidation of dialuric acid by the strong one-electron oxidant sulphate radical ions (SO4.-), and on the reduction of alloxan by the superoxide radical ions (O2.-). Time-resolved kinetic studies were carried out using conventional flash-photolysis equipment Xenon Co. model 720C with modified optics and electronics. The reactions of alloxan (A.H2O) with superoxide (k = (3.4 ± 0.5) × 106 M-1s-1) and carbon dioxide radical anions, and the reaction of dialuric acid (HA-) with sulphate radicals (k = (8 ± 1) × 107 M-1s-1) showed that the same radical (AH.) was formed either by the one-electron reduction of alloxan or by the one-electron oxidation of dialuric acid. A reaction mechanism involving several reversible reactions was proposed and validated. From the equilibrium constants involved, the reduction potentials for the redox couples alloxan/AH. and AH. /dialuric acid were calculated, E°(A.H2O/AH.) = -274 ±30 mV and E°(AH./HA-) = 244 ± 30 mV, respectively.