Commentary: On the merit of an early contributor of the "Preparation for Oxidative Stress" (POS) theory.

This commentary acknowledges the contributions of the Ukrainian biologist, Dr. Volodymyr Lushchak, to the understanding of the physiological adaptive strategy called "Preparation for Oxidative Stress" (POS). In the 1990s, various studies revealed that activities of antioxidant enzymes rose in animals under hypometabolic conditions. These timely observations allowed scientists to propose that this increase could prepare animals for reoxygenation events following the release of oxygen restriction, but in doing so, would trigger oxidative damage, hence the use of the term "preparation". Over next 25 years, the phenomenon was described in detail in more than one hundred studies of animals under conditions of aestivation, hypoxia/anoxia, freezing, severe dehydration, ultraviolet exposure, air exposure of water-breathing animals, salinity stress, and others. The POS phenomenon remained without a mechanistic explanation until 2013, when it was proposed that a small increase in oxyradical formation during hypoxia exposure (in hypoxia-tolerant animals) could activate redox-sensitive transcription factors that, in turn, would initiate transcription and translation of antioxidant enzymes. Dr. Lushchak, who studied goldfish under severe hypoxia in the 1990s, had actually proposed the increased production of oxyradicals under this condition and concluded that it would lead to an upregulation of antioxidant enzymes, the hallmark of the POS strategy. However, his research partner at the time, Dr. Hermes-Lima, thought the idea did not have sufficient evidence to support it and recommended the removal of this explanation. In those days, the main line of thinking was that increased oxyradical formation under hypoxia was "impossible". So, as it turns out, the ideas of Dr. Lushchak were well ahead of his time. It then took >10 years before the biochemical and molecular mechanisms responsible for triggering the POS response were clarified. In the present article, this fascinating history is described to highlight Dr. Lushchak's contributions and insights about the POS theory.