The Hyperoxic-Hypoxic Paradox

Amir Hadanny, Shai Efrati

Research output: Contribution to journalReview articlepeer-review


Effective metabolism is highly dependent on a narrow therapeutic range of oxygen. Accordingly, low levels of oxygen, or hypoxia, are one of the most powerful inducers of gene expression, metabolic changes, and regenerative processes, including angiogenesis and stimulation of stem cell proliferation, migration, and differentiation. The sensing of decreased oxygen levels (hypoxia) or increased oxygen levels (hyperoxia), occurs through specialized chemoreceptor cells and metabolic changes at the cellular level, which regulate the response. Interestingly, fluctuations in the free oxygen concentration rather than the absolute level of oxygen can be interpreted at the cellular level as a lack of oxygen. Thus, repeated intermittent hyperoxia can induce many of the mediators and cellular mechanisms that are usually induced during hypoxia. This is called the hyperoxic-hypoxic paradox (HHP). This article reviews oxygen physiology, the main cellular processes triggered by hypoxia, and the cascade of events triggered by the HHP.

Original languageEnglish
Issue number6
StatePublished - 25 Jun 2020

Bibliographical note

Funding Information:
Funding: The study was funded by a research grant from the Research fund of the Shamir medical center.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • biogenesis
  • hyperbaric oxygen
  • hyperoxia
  • hyperoxic-hypoxic paradox
  • hypoxia
  • hypoxia-inducible factor (HIF)


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