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

The toxic potential of H(2)O(2) is limited, even if intracellular concentrations of H(2)O(2) 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 H(2)O(2) 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, H(2)O(2) 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, H(2)O(2) is the pro-radical, that spreads the toxic action of the HO(·) radical. It is the longevity of the H(2)O(2) molecule allowing it to distribute its toxic action from the site of origin all over the cell and may even mediate intercellular communication. Thus, H(2)O(2) 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”. H(2)O(2) 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 H(2)O(2) inactivating enzyme capacity.