The pro-radical hydrogen peroxide as a stable hydroxyl radical distributor: lessons from pancreatic beta cells

The toxic potential of H₂O₂ is limited, even if intracellular concentrations of H₂O₂ under conditions of oxidative stress increase to the micromolar concentration range. Its toxicity is mostly restricted to the oxidation of highly reactive thiol groups, some of which are functionally very important. Subsequently, the HO^· radical is generated spontaneously from H₂O₂ in the Fenton reaction. The HO^· radical is extremely toxic and destroys any biological structure. Due to the high reactivity, its action is limited to a locally restricted site of its generation. On the other hand, H₂O₂ with its stability and long half-life can reach virtually any site and distribute its toxic effect all over the cell. Thereby HO^·, in spite of its ultra-short half-life (10^-9 s), can execute its extraordinary toxic action at any target of the cell. In this oxidative stress scenario, H₂O₂ is the pro-radical, that spreads the toxic action of the HO^· radical. It is the longevity of the H₂O₂ molecule allowing it to distribute its toxic action from the site of origin all over the cell and may even mediate intercellular communication. Thus, H₂O₂ acts as a spreader by transporting it to sites where the extremely short-lived toxic HO^· radical can arise in the presence of "free iron". H₂O₂ and HO^· act in concert due to their different complementary chemical properties. They are dependent upon each other while executing the toxic effects in oxidative stress under diabetic metabolic conditions in particular in the highly vulnerable pancreatic beta cell, which in contrast to many other cell types is so badly protected against oxidative stress due to its extremely low H₂O₂ inactivating enzyme capacity.