CELLULAR REDUCING EQUIVALENTS AND OXIDATIVE STRESS

Energy has been proposed to play a role in the ability of cells and ti ssues to defend against oxidative stress, even though the ultimate ant ioxidant capacity of a tissue is determined by the supply of reducing equivalents. The pathways involved in supplying reducing equivalents i n response to an oxidative stress remain unclear, particularly if comp eting reactions such as ATP synthesis are active. Glutathione (GSH), a major component of cellular antioxidant systems, is maintained in the reduced form by glutathione reductase. Although this enzyme is specif ic for NADPH, the ability of intact cells, isolated mitochondria (whic h are a major source of free radicals and contain antioxidant systems independent of the rest of the cell), and whole tissues to supply redu cing equivalents and maintain normal levels of GSH appears to involve NADH. This article reviews available data regarding the source and pat hways by which reducing equivalents are made available to reduce exoge nous oxidants, and suggests energy is not a factor. An improved unders tanding of the mechanism by which reducing equivalents are supplied by tissues to respond to an oxidative stress may direct future research toward designing strategies for augmenting the ability of tissues to d efend themselves against oxidative stress induced by reperfusion or xe nobiotics.