Hypoxia may be intensified by concurrent oxidative stress. Lack of oxygen in relation to aerobic ATP requirements, as hypoxia has been defined, goes along with an increased generation of reactive oxygen species (ROS). Polyunsaturated fatty acids (PUFAs) range among the molecules most susceptible to ROS. Oxidative breakdown of n-3 PUFAs may compromise not only membrane lipid matrix dynamics, and hence structure and function of membrane-associated proteins like enzymes, receptors, and transporters, but also gene expression. Eicosapentaenoic acid depletion, products of lipid peroxidation (LP), as well as, lack of oxygen may combine in exacerbating activity of nuclear factor kappa B (NFκB), an ubiquitous pro-inflammatory and anti-apoptotic transcription factor. Field studies at high altitude show malondialdehyde (MDA) content in exhaled breath condensate (EBC) of mountaineers to correlate with Lake Louis score of acute mountain sickness. A pathogenic role of LP in hypoxia can therefore be expected. By control of LP, some species seem to cope more efficiently than others with naturally occurring hypoxia. Limitation of potential pro-inflammatory effects of hypoxia-related LP by an adequate provision of n-3 PUFAs and antioxidants may contribute to increase survival under conditions where oxygen is lacking in relation to aerobic ATP requirements. A need for antioxidant intervention, however, should be weighed against the ROS requirement for triggering adaptive processes in response to an increased demand of oxygen.
Bibliographical noteFunding Information:
FONDECYT 1000858 and DIPUV grant 31/2001 have supported the work of C.B., G.C. and G.G. C.B. also acknowledges network formation by ALFA HAPPOM II-0379-FCD. The authors thank the Chilean Air Force and the Chilean Army for access to humans exposed for professional reasons to hypobaric environments, either in the laboratory or in the field. They are, moreover, very much indebted to Professor Dr. L.A. Videla for reviewing the manuscript and helpful advice.
- Acute mountain sickness
- High altitude
- Hypobaric hypoxia
- Lipid peroxidation
- Nuclear factor kappa B
- Oxidative stress
- Oxygen sensing
- Reactive oxygen species
- n-3 polyunsaturated fatty acids