ABSTRACT
Life on Earth has evolved on the foundation of two main processes: (a) photosynthesizing organisms (plants) that capture solar energy and use it to promote thermodynamically unfavorable reactions leading to the reduction of carbon substances, and (b) organisms that receive the above produced reduced compounds and oxidize them in thermodynamically favorable reactions. The latter processes release large amounts of energy that are captured in the form of chemical energy and used then as the power that supports the maintenance of life. The electrons used for the reductive processes in photosynthetic plants are released during the oxidation of the H2O to O2, whereas in the catabolic processes the opposite direction is followed by reduction of molecular oxygen (O2) to water (H2O) (Scheme 16.1). The latter reaction is catalyzed by the last enzyme of the respiratory chain, namely cytochrome oxidase (complex IV), which binds molecular oxygen in its active site and reduces it to H2O
An Introduction to Oxidative Stress ......................................................................227 Generation of Reactive Oxygen Species ................................................................228 Hydrogen Peroxide ................................................................................................. 229 Hydrogen Peroxide-Induced DNA Damage .......................................................... 229 Detection of Single Strand Breaks .........................................................................230 Protection By Iron Chelators .................................................................................230 The Action of Desferrioxamine ............................................................................. 231 Conclusions ............................................................................................................ 236 References .............................................................................................................. 236
by donating four electrons without any release of partially reduced intermediates. However, a small part of the oxygen consumed by mitochondria (usually about 2-4%) is reduced, even under normal conditions, by single electrons leading to the formation of a variety of reactive oxygen intermediates (Scheme 16.2). In this way, aerobic organisms are continuously exposed to endogenously generated reactive oxygen species (ROS) and in spite of the existed anti-oxidant defenses, a steady-state concentration of ROS is always present.1 In addition, a number of pathological conditions have been shown to be intimately connected to increased steady-state
levels of ROS which may be the result of either an increased rate of production or a decreased ability for the removal of these species.2-5 This temporary imbalance of cellular redox equilibrium is usually defined as “oxidative stress.”6 This imbalance of the cellular redox equilibrium is not, as believed before, an unavoidable side effect of oxygen metabolism but rather it appears to be a carefully regulated process, capable of transferring important signals from cell surface toward the genetic machinery of the cell.7 Today, redox regulation of gene expression is regarded as a vital mechanism involved in a number of pathophysiological complications in humans and animals.8,9
Oxygen, due to its ubiquitous appearance in biological materials and its ability to accept single electrons from other compounds represents the main source of reactive species in cells. One electron reduction of oxygen leads to the formation of superoxide radicals (O2.−) whereas, when it is reduced by two electrons, the product is hydrogen peroxide (H2O2). It has to be noted that the latter compound is not a free radical, but it can participate in processes that contribute to formation of free radicals. Ferrous iron, cuprous copper, and several other transition metals are able
to donate a third electron to H2O2, causing the breakage of the O-O bond. In these cases the one part of the molecule is reduced to the state of water while the other part forms the extremely reactive hydroxyl radical (.OH). The latter is one of the most potent oxidants known, reacting indiscriminately with any organic molecule that is going to be in the vicinity of its generation.
