Abstract

See related article, pages 310–318 Although the Greek physician Galenos (129 to 216 AD) recognized early that ventilation of the lungs is important for the transfer of an unknown substance from the air into the blood, it took surprisingly long to discover that oxygen is a major “fuel” for our metabolism that oxidizes nutrients to generate chemical energy. Even William Harvey in his famous work about the circulatory system published in 1628 thought that respiration was necessary solely for cooling down the blood, ie, preventing it from burning. He explicitly disputed that the lungs are responsible for the transport of “spirit,” a hypothetical substance thought to be essential for life.1 Not until 1788, shortly before his execution in the turmoil of the French revolution, the chemist Antoine Laurent de Lavoisier (who had discovered oxygen some 10 years before) stated “ … that is, respiratory gas exchange is a combustion, like that of a candle burning”.2,3 However, apart from truly being the spirit of our life, oxygen is a rather harmful and dangerous compound that may be illustrated best by the fact that chemical reactions in which electrons are captured from a molecule are referred to as oxidations. In our body, biological macromolecules are effectively shielded from oxygen and oxygen-derived radicals by a multitude of both specific and nonspecific protective mechanisms, including uric acid, glutathione, the thioredoxins, or enzymes, including the superoxide dismutases or catalase, to name a few.4 Surprisingly, it was only 20 years ago or so when it was realized that molecular oxygen not only reacts with cellular components but also gives rise to the formation of reactive oxygen species (ROS), acting both as powerful defensive arms against invading microorganisms and as intercellular and intracellular signaling molecules. Most prominent among these ROS is the superoxide …

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