Use and abuse of exogenous H2O2 in studies of signal transduction

The goal of this review is to present a rationale for the use of exogenous H(2)O(2), which has been demonstrated to have both toxicological and physiological signaling roles. Reasons for the use of exogenous application of nontoxic concentrations of H(2)O(2) in model systems and caveats for interpretation of the data obtained will both be presented. Briefly, an argument for the cautious use of the addition of exogenous H(2)O(2) is that, because of the permeability of cell membranes to this neutral small molecule, a concentration that is produced locally and that is necessary for the physiological action can be mimicked. On the other hand, it must be recognized that the addition of an agent or its enzymatic generation in the medium may produce reactions that may not normally occur because the total dose of H(2)O(2) and the concentration of H(2)O(2) in some cellular locations will exceed what is normally achieved even under a pathophysiological state. For this reason, this review will try to provide an unbiased balanced pros- and -cons analysis of this issue.