Skip to main content
SpringerLink
Log in

The Effects of High-Altitude Exposure on Reactive Oxygen and Nitrogen Species

  • Reference work entry
  • First Online:
Systems Biology of Free Radicals and Antioxidants

Abstract

High-altitude exposure that results in decreased levels of oxygen pressure, which could lead to hypoxia, can activate a number of sources that can generate reactive oxygen and nitrogen species (RONS). Enhanced formation of RONS causes oxidative damage, which impacts cellular function and could seriously impair organ function. In addition, high altitude appears to weaken the enzymatic and nonenzymatic antioxidant systems. Indeed, recent data suggest that the expression of Mn-SOD in skeletal muscle of mountaineers, who stayed for more than 6 weeks above 6,000 m, decreased significantly 1 week after leaving that altitude. Moreover, the expression of Ku70, which plays an important role in DNA repair, increased after exposure to high altitude, indicating increased DNA damage. Therefore, it appears that increased nutritional uptake of antioxidant vitamins reduce altitude-induced oxidative damage. The pattern of high-altitude exposure-associated oxidative damage is similar to ischemia/reperfusion injury. The adaptive process for this oxidative challenge is relatively long, and physical exercise or enhanced levels of physical activity at high altitude exacerbate the extent of the oxidative challenge. Therefore, special attention must be given to any and all processes which modulate the degree of oxidative stress.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,999.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 2,999.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Askew EW (2002) Work at high altitude and oxidative stress: antioxidant nutrients. Toxicology 180:107–119

    Article  CAS  PubMed  Google Scholar 

  • Bailey DM, Davies B (2001) Acute mountain sickness; prophylactic benefits of antioxidant vitamin supplementation at high altitude. High Alt Med Biol 2:21–29

    Article  CAS  PubMed  Google Scholar 

  • Bailey DM, Davies B, Young IS, Hullin DA, Seddon PS (2001) A potential role for free radical-mediated skeletal muscle soreness in the pathophysiology of acute mountain sickness. Aviat Space Environ Med 72:513–521

    CAS  PubMed  Google Scholar 

  • Bailey DM, Bartsch P, Knauth M, Baumgartner RW (2009) Emerging concepts in acute mountain sickness and high-altitude cerebral edema: from the molecular to the morphological. Cell Mol Life Sci 66:3583–3594

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chao WH, Askew EW, Roberts DE, Wood SM, Perkins JB (1999) Oxidative stress in humans during work at moderate altitude. J Nutr 129:2009–2012

    CAS  PubMed  Google Scholar 

  • Faoro V, Fink B, Taudorf S, Dehnert C, Berger MM, Swenson ER, Bailey DM, Bartsch P, Mairbaurl H (2011) Acute in vitro hypoxia and high-altitude (4,559 m) exposure decreases leukocyte oxygen consumption. Am J Physiol Regul Integr Comp Physiol 300:R32–R39

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez NC, Wood JG (2001) Leukocyte-endothelial interactions in environmental hypoxia. Adv Exp Med Biol 502:39–60

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez G, Celedon G, Escobar M, Sotomayor C, Ferrer V, Benitez D, Behn C (2005) Red cell membrane lipid changes at 3,500 m and on return to sea level. High Alt Med Biol 6:320–326

    Article  CAS  PubMed  Google Scholar 

  • Ilavazhagan G, Bansal A, Prasad D, Thomas P, Sharma SK, Kain AK, Kumar D, Selvamurthy W (2001) Effect of vitamin E supplementation on hypoxia-induced oxidative damage in male albino rats. Aviat Space Environ Med 72:899–903

    CAS  PubMed  Google Scholar 

  • Imai H, Kashiwazaki H, Suzuki T, Kabuto M, Himeno S, Watanabe C, Moji K, Kim SW, Rivera JO, Takemoto T (1995) Selenium levels and glutathione peroxidase activities in blood in an Andean high-altitude population. J Nutr Sci Vitaminol (Tokyo) 41:349–361

    Article  CAS  Google Scholar 

  • Joanny P, Steinberg J, Robach P, Richalet JP, Gortan C, Gardette B, Jammes Y (2001) Operation Everest III (Comex’97): the effect of simulated sever hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise. Resuscitation 49:307–314

    Article  CAS  PubMed  Google Scholar 

  • Khan S, O’Brien PJ (1995) Modulating hypoxia-induced hepatocyte injury by affecting intracellular redox state. Biochim Biophys Acta 1269:153–161

    Article  PubMed  Google Scholar 

  • Kumar D, Bansal A, Thomas P, Sairam M, Sharma SK, Mongia SS, Singh R, Selvamurthy W (1999) Biochemical and immunological changes on oral glutamate feeding in male albino rats. Int J Biometeorol 42:201–204

    Article  CAS  PubMed  Google Scholar 

  • Maiti P, Singh SB, Sharma AK, Muthuraju S, Banerjee PK, Ilavazhagan G (2006) Hypobaric hypoxia induces oxidative stress in rat brain. Neurochem Int 49:709–716

    Article  CAS  PubMed  Google Scholar 

  • Mariggio MA, Falone S, Morabito C, Guarnieri S, Mirabilio A, Pilla R, Bucciarelli T, Verratti V, Amicarelli F (2010) Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude. High Alt Med Biol 11:333–342

    Article  PubMed  Google Scholar 

  • Mishra A, Ali Z, Vibhuti A, Kumar R, Alam P, Ram R, Thinlas T, Mohammad G, Pasha MA (2012) CYBA and GSTP1 variants associate with oxidative stress under hypobaric hypoxia as observed in high-altitude pulmonary oedema. Clin Sci (Lond) 122:299–309

    Article  CAS  Google Scholar 

  • Mitteldorf J (2010) Aging is not a process of wear and tear. Rejuvenation Res 13:322–326

    Article  PubMed  Google Scholar 

  • Mohanraj P, Merola AJ, Wright VP, Clanton TL (1998) Antioxidants protect rat diaphragmatic muscle function under hypoxic conditions. J Appl Physiol 84:1960–1966

    CAS  PubMed  Google Scholar 

  • Moller P, Loft S, Lundby C, Olsen NV (2001) Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans. FASEB J 15:1181–1186

    Article  CAS  PubMed  Google Scholar 

  • Nakanishi K, Tajima F, Nakamura A, Yagura S, Ookawara T, Yamashita H, Suzuki K, Taniguchi N, Ohno H (1995) Effects of hypobaric hypoxia on antioxidant enzymes in rats. J Physiol 489(Pt 3):869–876

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nugroho A, Kim KH, Lee KR, Alam MB, Choi JS, Kim WB, Park HJ (2009) Qualitative and quantitative determination of the caffeoylquinic acids on the Korean mountainous vegetables used for chwinamul and their peroxynitrite-scavenging effect. Arch Pharm Res 32:1361–1367

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffer JM, Askew EW, Roberts DE, Wood SM, Benson JE, Johnson SC, Freedman MS (1999) Effect of antioxidant supplementation on urine and blood markers of oxidative stress during extended moderate-altitude training. Wilderness Environ Med 10:66–74

    Article  CAS  PubMed  Google Scholar 

  • Radak Z, Lee K, Choi W, Sunoo S, Kizaki T, Oh-ishi S, Suzuki K, Taniguchi N, Ohno H, Asano K (1994) Oxidative stress induced by intermittent exposure at a simulated altitude of 4000 m decreases mitochondrial superoxide dismutase content in soleus muscle of rats. Eur J Appl Physiol Occup Physiol 69:392–395

    Article  CAS  PubMed  Google Scholar 

  • Radak Z, Asano K, Inoue M, Kizaki T, Oh-Ishi S, Suzuki K, Taniguchi N, Ohno H (1995) Superoxide dismutase derivative reduces oxidative damage in skeletal muscle of rats during exhaustive exercise. J Appl Physiol 79:129–135

    CAS  PubMed  Google Scholar 

  • Radak Z, Asano K, Lee KC, Ohno H, Nakamura A, Nakamoto H, Goto S (1997) High altitude training increases reactive carbonyl derivatives but not lipid peroxidation in skeletal muscle of rats. Free Radic Biol Med 22:1109–1114

    Article  CAS  PubMed  Google Scholar 

  • Radak Z, Asano K, Fu Y, Nakamura A, Nakamoto H, Ohno H, Goto S (1998) The effect of high altitude and caloric restriction on reactive carbonyl derivatives and activity of glutamine synthetase in rat brain. Life Sci 62:1317–1322

    Article  CAS  PubMed  Google Scholar 

  • Radak Z, Taylor AW, Ohno H, Goto S (2001) Adaptation to exercise-induced oxidative stress: from muscle to brain. Exerc Immunol Rev 7:90–107

    CAS  PubMed  Google Scholar 

  • Scherrer U, Allemann Y, Jayet PY, Rexhaj E, Sartori C (2010a) High altitude, a natural research laboratory for the study of cardiovascular physiology and pathophysiology. Prog Cardiovasc Dis 52:451–455

    Article  PubMed  Google Scholar 

  • Scherrer U, Rexhaj E, Jayet PY, Allemann Y, Sartori C (2010b) New insights in the pathogenesis of high-altitude pulmonary edema. Prog Cardiovasc Dis 52:485–492

    Article  PubMed  Google Scholar 

  • Schmidt MC, Askew EW, Roberts DE, Prior RL, Ensign WY Jr, Hesslink RE Jr (2002) Oxidative stress in humans training in a cold, moderate altitude environment and their response to a phytochemical antioxidant supplement. Wilderness Environ Med 13:94–105

    Article  PubMed  Google Scholar 

  • Schneider JC, Blazy I, Dechaux M, Rabier D, Mason NP, Richalet JP (2001) Response of nitric oxide pathway to l-arginine infusion at the altitude of 4,350 m. Eur Respir J 18:286–292

    Article  CAS  PubMed  Google Scholar 

  • Serrano J, Encinas JM, Salas E, Fernandez AP, Castro-Blanco S, Fernandez-Vizarra P, Bentura ML, Rodrigo J (2003) Hypobaric hypoxia modifies constitutive nitric oxide synthase activity and protein nitration in the rat cerebellum. Brain Res 976:109–119

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Singh SN, Ray US (2009) Total antioxidant status at high altitude in lowlanders and native highlanders: role of uric acid. High Alt Med Biol 10:269–274

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Dutta A, Singh SN, Ray US (2010) Protein nitration, lipid peroxidation and DNA damage at high altitude in acclimatized lowlanders and native highlanders: relation with oxygen consumption. Respir Physiol Neurobiol 171:115–121

    Article  CAS  PubMed  Google Scholar 

  • Subudhi AW, Jacobs KA, Hagobian TA, Fattor JA, Muza SR, Fulco CS, Cymerman A, Friedlander AL (2006) Changes in ventilatory threshold at high altitude: effect of antioxidants. Med Sci Sports Exerc 38:1425–1431

    Article  CAS  PubMed  Google Scholar 

  • Tharakan B, Dhanasekaran M, Manyam BV (2005) Antioxidant and DNA protecting properties of anti-fatigue herb Trichopus zeylanicus. Phytother Res 19:669–673

    Article  PubMed  Google Scholar 

  • Vij AG, Dutta R, Satija NK (2005) Acclimatization to oxidative stress at high altitude. High Alt Med Biol 6:301–310

    Article  CAS  PubMed  Google Scholar 

  • Wilber RL, Holm PL, Morris DM, Dallam GM, Subudhi AW, Murray DM, Callan SD (2004) Effect of FIO2 on oxidative stress during interval training at moderate altitude. Med Sci Sports Exerc 36:1888–1894

    Article  CAS  PubMed  Google Scholar 

  • Wozniak A, Drewa G, Chesy G, Rakowski A, Rozwodowska M, Olszewska D (2001) Effect of altitude training on the peroxidation and antioxidant enzymes in sportsmen. Med Sci Sports Exerc 33:1109–1113

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Insitute of Sport Science, Faculty of Physical Education and Sport Science, Semmelweis University, Budapest, Hungary

    Zsolt Radak, Zoltan Acs & Zoltan Bori

  2. School of Kinesiology, Faculty of Health Sciences and Department of Physiology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Canada

    Albert W. Taylor

  3. Research Institute, Beijing Sport University, Beijing, China

    Hu Yang

Authors
  1. Zsolt Radak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zoltan Acs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zoltan Bori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Albert W. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zsolt Radak , Zoltan Acs , Zoltan Bori , Albert W. Taylor or Hu Yang .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Radak, Z., Acs, Z., Bori, Z., Taylor, A.W., Yang, H. (2014). The Effects of High-Altitude Exposure on Reactive Oxygen and Nitrogen Species. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_28

Download citation

Publish with us

Policies and ethics

Search

Navigation