ABSTRACT
The earth formed approximately 4.5 billion years ago and unicellular organisms, which received their nutrients from surrounding media, appeared approximately one billion years later.1 It has been estimated that the earth was anoxic for at least 2 billion years. Around 2.3 billion years ago, there was a sudden increase in oxygen in the oceans and atmosphere. It is thought that the first photosynthetic organisms, cyanobacteria, were responsible for this ‘great oxidation event’; however, there was also depletion of other gases, such as methane and hydrogen, which permitted oxygen to accumulate.2 The appearance of oxygen on the surface of the earth subsequently triggered the development of complex multicellular organisms that could utilize oxygen.3 The symbiotic relationship that subsequently evolved between plants and animals served both kingdoms well in the ensuing millions of years; however, a very complex biology arose as a result of this dependence on oxygen. Prokaryotic and eukaryotic cells adapted small molecules as antioxidants and developed enzymes that produce, scavenge and utilize reactive oxygen species (ROS) and other enzymes that can repair oxidative damage. Interestingly, some of these enzymes are highly preserved from bacteria to man, supporting the concept that the co-existence with oxygen metabolites has been essential for millions of years. Further and not well understood, eukaryotic cells have begun to use ROS and their targets as signaling molecules. This latter phenomenon has radically changed our view and treatment of oxidative injury, because we now realize that removal of all oxygen metabolites could have untoward effects.
