Free radicals and oxidative damage in biology and medicine: An introduction

When living organisms first evolved on the Earth, they did so under an atmosphere containing very little O2, i.e. they were essentially anaerobes. Anaerobic micro-organisms still survive to this day, but their growth is inhibited and they can often be killed by exposure to 21% O2, the current atmospheric level. As the O2 content of the atmosphere rose (as a result of the evolution of organisms with photosynthetic water-splitting capacity), many primitive organisms must have died. Present-day anaerobes are presumably the descendants of those primitive organisms that followed the evolutionary path of "adapting" to rising atmospheric O2 levels by restricting themselves to environments that the O2 did not penetrate. However, other organisms began the evolutionary process of evolving antioxidant defence systems to protect against O2 toxicity. In retrospect, this was a fruitful path to follow. Organisms that tolerated the presence of O2 could also evolve to use it for metabolic transformations (oxidases, oxygenases and synthases such as nitric oxide synthase [NOS]) and for efficient energy production by using electron transport chains with O2 as the terminal electron acceptor, such as those present in mitochondria. Human mitochondria make over 80% of the ATP that we need, and the lethal effects of inhibiting this, e.g. by cyanide, show how important the mitochondria are. Mitochondrial defects contribute to the pathology of a wide range of diseases, as shown in subsequent chapters of this book.