Skip to main content
Log in

Physiological significance of oxidative stress and its role in adaptation of the human body to deleterious factors

  • Review
  • Published:
Frontiers in Biology

Abstract

Background

Oxidative stress is an extremely widespread condition manifested in an increased rate of free-radical processes and accumulation of reactive oxygen species (ROS) in the tissues. It appears in different physiologic states and pathological processes accompanied by stimulation of the sympathetic adrenal system or tissue hypoxia or under stress. However, until now, there is still no clarity on the issue of the significance of oxidative stress in the development of adaptation processes in the organism.

Objective

In the present work we will review the most recent finding about physiologic role of oxidative stress and its participation in adaptation of an organism to effect of different adverse factors.

Methods

A systematic literature search was performed using the Pubmed search engine. Studies published over past 18 years, i.e. between 1998 and 2015 were considered for review. Followed keywords were used: “oxidative stress,” “free radical oxidation,” “ROS,” “endogenous aldehydes,” “adaptation.”

Results

The article cites arguments supporting the notion that oxidative stress serves as a nonspecific link in the adaptation of the human body to the effects of injurious factors. Oxidative stress exerts regulatory effects by changing the redox state of the cell. Oxidative stress affects on various intracellular proteins containing cysteine residues, e.g., enzymes, chaperones, and transcription factors, etc. For this reason, the use of antioxidants for the treatment and prophylaxis of a wide range of diseases is not recommended.

Conclusion

Further investigation is needed in this field. The most attention should be paid to careful experimental verification aimed at quantitative assessment of the ROS level in tissues under oxidative stress, as well as at the study of possibility of enhancing the catabolism of free radical oxidation carbonyl products in order to prevent tissue damage under oxidative stress.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Afroze T, Sadi A M, Momen M A, Gu S, Heximer S, Husain M (2007). c-Myb-dependent inositol 1,4,5-trisphosphate receptor type-1 expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol, 27(6): 1305–1311

    Article  PubMed  CAS  Google Scholar 

  • Akhtar M, Wright J N (2015). Acyl-Carbon Bond Cleaving Cytochrome P450 Enzymes: CYP17A1, CYP19A1 and CYP51A1. Adv Exp Med Biol, 851: 107–130

    Article  PubMed  CAS  Google Scholar 

  • Antelmann H, Helmann J D (2011). Thiol-based redox switches and gene regulation. Antioxid Redox Signal, 14(6): 1049–1063

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Basse A L, Isidor M S, Winther S, Skjoldborg N B, Murholm M, Andersen E S, Pedersen S B, Wolfrum C, Quistorff B, Hansen J B (2017). Regulation of glycolysis in brown adipocytes by HIF-1a. Sci Rep, 7(1): 4052

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Baud O, Greene A E, Li J, Wang H, Volpe J J, Rosenberg P A (2004). Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes. J Neurosci, 24(7): 1531–1540

    Article  PubMed  CAS  Google Scholar 

  • Becker L B (2004). New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc Res, 61 (3): 461–470

    Article  PubMed  CAS  Google Scholar 

  • Betteridge D J (2000). What is oxidative stress? Metabolism, 49(2 Suppl 1): 3–8

    Article  PubMed  CAS  Google Scholar 

  • Bleier L, Wittig I, Heide H, Steger M, Brandt U, Dröse S (2015). Generator-specific targets of mitochondrial reactive oxygen species. Free Radic Biol Med, 78: 1–10

    Article  PubMed  CAS  Google Scholar 

  • Brandes N, Schmitt S, Jakob U (2009). Thiol-based redox switches in eukaryotic proteins. Antioxid Redox Signal, 11(5): 997–1014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brown D I, Griendling K K (2015). Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res, 116 (3): 531–549

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chandel N S, Tuveson D A (2014). The promise and perils of antioxidants for cancer patients. N Engl J Med, 371(2): 177–178

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, AzadMB, Gibson S B (2009). Superoxide is the major reactive oxygen species regulating autophagy. Cell Death Differ, 16(7): 1040–1052

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Xu H, Liu J, Zhang C, Leutz A, Mo X (2007). The c-Myb functions as a downstream target of PDGF-mediated survival signal in vascular smooth muscle cells. Biochem Biophys Res Commun, 360(2): 433–436

    Article  PubMed  CAS  Google Scholar 

  • Chen Y R, Zweier J L (2014). Cardiac mitochondria and ROS generation. Circ Res, 114(3): 524–537

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheng Y, Chen G, Hong L, Zhou L, Hu M, Li B, Huang J, Xia L, Li C (2013). How does hypoxia inducible factor-1a participate in enhancing the glycolysis activity in cervical cancer? Ann Diagn Pathol, 17(3): 305–311

    Article  PubMed  Google Scholar 

  • Collins Y, Chouchani E T, James A M, Menger K E, Cochemé H M, Murphy M P (2012). Mitochondrial redox signalling at a glance. J Cell Sci, 125(Pt 4): 801–806

    Article  PubMed  CAS  Google Scholar 

  • Corre S, Galibert M D (2005). Upstream stimulating factors: highly versatile stress-responsive transcription factors. Pigment Cell Res, 18 (5): 337–348

    Article  PubMed  CAS  Google Scholar 

  • Corre S, Galibert M D (2006). [USF as a key regulatory element of gene expression]. Med Sci (Paris), 22(1): 62–67

    Article  Google Scholar 

  • Cox A G, Winterbourn C C, Hampton M B (2009). Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem J, 425(2): 313–325

    Article  PubMed  CAS  Google Scholar 

  • D’Autréaux B, Toledano M B (2007). ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol, 8(10): 813–824

    Article  PubMed  CAS  Google Scholar 

  • Davydov V V (2014). Age-dependent change in aldo-keto reductases composition in the blood of rats. Am J Biomed Life Sci, 2(1): 1–4

    Article  CAS  Google Scholar 

  • Davydov V V, Bozhkov A I, Grabovetskaya E R (2014). Age-related peculiarities of change in content of free radical oxidation products in muscle during stress. Fron Biol, 9(4): 283–286

    Article  CAS  Google Scholar 

  • Davydov V V, Bozhkov A I, Kulchitskiy O K (2012). Physiological and pathophysiological role of endogenous aldehydes, Saarbrucken: Palmarium Academic Publishing, 240 (inRussian)

    Google Scholar 

  • Davydov V V, Dobaeva N M, Bozhkov A I (2004). Possible role of alteration of aldehyde’s scavenger enzymes during aging. Exp Gerontol, 39(1): 11–16

    Article  PubMed  CAS  Google Scholar 

  • Davydov V V, Shvets V N (2001). Lipid peroxidation in the heart of adult and old rats during immobilization stress. Exp Gerontol, 36(7): 1155–1160

    Article  PubMed  CAS  Google Scholar 

  • Davydov V V, Shvets V N (2003). Age-dependent differences in the stimulation of lipid peroxidation in the heart of rats during immobilization stress. Exp Gerontol, 38(6): 693–698

    Article  PubMed  CAS  Google Scholar 

  • Dröge W (2002). Free radicals in the physiological control of cell function. Physiol Rev, 82(1): 47–95

    Article  PubMed  Google Scholar 

  • Dröse S, Brandt U, Wittig I (2014). Mitochondrial respiratory chain complexes as sources and targets of thiol-based redox-regulation. Biochim Biophys Acta, 1844(8): 1344–1354

    Article  PubMed  CAS  Google Scholar 

  • Farrell K A,Withers S B, Holt CM (2011). C-Myb function in the vessel wall. Front Biosci (Elite Ed), 3: 968–977

    Google Scholar 

  • Finkel T (2011). Signal transduction by reactive oxygen species. J Cell Biol, 194(1): 7–15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fridovich I (1999). Fundamental aspects of reactive oxygen species, or what’s the matter with oxygen? Ann N Y Acad Sci, 893(1 OXIDATIVE/ENE): 13–18

    Article  PubMed  CAS  Google Scholar 

  • Giles G I (2006). The redox regulation of thiol dependent signaling pathways in cancer. Curr Pharm Des, 12(34): 4427–4443

    Article  PubMed  CAS  Google Scholar 

  • Groitl B, Jakob U (2014). Thiol-based redox switches. Biochim Biophys Acta, 1844(8): 1335–1343

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Halliwell B (2009). The wanderings of a free radical. Free Radic Biol Med, 46(5): 531–542

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (2012). Free radicals and antioxidants: updating a personal view. Nutr Rev, 70(5): 257–265

    Article  PubMed  Google Scholar 

  • Harman D (1956). Aging: a theory based on free radical and radiation chemistry. J Gerontol, 11(3): 298–300

    Article  PubMed  CAS  Google Scholar 

  • Hinerfeld D, Traini M D, Weinberger R P, Cochran B, Doctrow S R, Harry J, Melov S (2004). Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. J Neurochem, 88(3): 657–667

    Article  PubMed  CAS  Google Scholar 

  • Hirano F, Tanaka H, Hirano Y, Hiramoto M, Handa H, Makino I, Scheidereit C (1998). Functional interference of Sp1 and NF-kappaB through the same DNA binding site. Mol Cell Biol, 18(3): 1266–1274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Imlay J A (2008). Cellular defenses against superoxide and hydrogen peroxide. Annu Rev Biochem, 77(1): 755–776

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jomova K, Valko M (2011). Advances in metal-induced oxidative stress and human disease. Toxicol, 283 (2–3): 65–87

    Article  CAS  Google Scholar 

  • Kuntsevich N V (2010). The role of nuclear factor Nf-b in the rejection of transplatant. Vestnik transplantology and artifical organs, 1: 72–77 (in Russian)

    Google Scholar 

  • Leonarduzzi G, Sottero B, Poli G (2010). Targeting tissue oxidative damage by means of cell signaling modulators: the antioxidant concept revisited. Pharmacol Ther, 128(2): 336–374

    Article  PubMed  CAS  Google Scholar 

  • Leonarduzzi G, Sottero B, Testa G, Biasi F, Poli G (2011). New insights into redox-modulated cell signaling. Curr Pharm Des, 17(36): 3994–4006

    Article  PubMed  CAS  Google Scholar 

  • Ma Q (2013). Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol, 53(1): 401–426

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ma Q, and Ma Q (2008). Xenobiotic-activated receptors: from transcription to drug metabolism to disease. Chem Res Toxicol, 21 (9): 1651–1671

    Article  PubMed  CAS  Google Scholar 

  • Marín-Hernández A, Gallardo-Pérez J C, Ralph S J, Rodríguez-Enríquez S, Moreno-Sánchez R (2009). HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem, 9(9): 1084–1101

    Article  PubMed  Google Scholar 

  • Meerson F Z (1984). Pathogenesis and prevention of stress and ischemic injures of heart. Moscow. Medicina (B Aires), 270 (in Russian)

    Google Scholar 

  • Menshikova E B, Lankin V Z, Zenkov N K (2006). The oxidative stress. Antioxidants and prooxidants. Moscow: Slovo, 556 (in Russian)

    Google Scholar 

  • Miki H, Funato Y (2012). Regulation of intracellular signalling through cysteine oxidation by reactive oxygen species. J Biochem, 151(3): 255–261

    Article  PubMed  CAS  Google Scholar 

  • Montuschi P, Barnes P, Roberts L J 2nd (2007). Insights into oxidative stress: the isoprostanes. Curr Med Chem, 14(6): 703–717

    Article  PubMed  CAS  Google Scholar 

  • Morigasaki S, Shimada K, Ikner A, Yanagida M, Shiozaki K (2008). Glycolytic enzyme GAPDH promotes peroxide stress signaling through multistep phosphorelay to a MAPK cascade. Mol Cell, 30 (1): 108–113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Muller F L, Lustgarten M S, Jang Y, Richardson A, Van Remmen H (2007). Trends in oxidative aging theories. Free Radic Biol Med, 43 (4): 477–503

    Article  PubMed  CAS  Google Scholar 

  • Myung S K, Ju W, Cho B, Oh S W, Park S M, Koo B K, Park B J, and the Korean Meta-Analysis Study Group (2013). Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ, 346(jan18 1): f10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nayanatara A K, Nagaraja H S, Anupama B K (2005). The effect of repeated swimming stress on organ weights and lipid peroxidation in rats. Thai J Physiol Sci, 18(1): 3–9

    Google Scholar 

  • Nietzel T, Mostertz J, Hochgräfe F, Schwarzländer M (2017). Redox regulation of mitochondrial proteins and proteomes by cysteine thiol switches. Mitochondrion, 33: 72–83

    Article  PubMed  CAS  Google Scholar 

  • O’Brein PJO, Siraki A G, Shangari N (2005). Aldehyde sources metabolism, molecular toxicity mechanisms,and possible effects on human health. Critical Reviews inToxicology, 35: 609–662

    Article  CAS  Google Scholar 

  • Piwowar A (2010). [Advanced oxidation protein products. Part I. Mechanism of the formation, characteristics and property]. Pol Merkur Lekarski, 28(164): 166–169

    PubMed  CAS  Google Scholar 

  • Plotnikov E Y, Silachev D N, Jankauskas S S, Rokitskaya T I, Chupyrkina A A, Pevzner I B, Zorova L D, Isaev N K, Antonenko Y N, Skulachev V P, Zorov D B (2012). Mild uncoupling of respiration and phosphorylation as a mechanism providing nephro-and neuroprotective effects of penetrating cations of the SkQ family. Biochemistry (Mosc), 77(9): 1029–1037

    Article  CAS  Google Scholar 

  • Poyton R O, Ball K A, Castello P R (2009). Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab, 20(7): 332–340

    Article  PubMed  CAS  Google Scholar 

  • Reczek C R, Chandel N S (2015). ROS-dependent signal transduction. Curr Opin Cell Biol, 33: 8–13

    Article  PubMed  CAS  Google Scholar 

  • Roginsky V A, Tashlitsky V N, Skulachev V P (2009). Chain-breaking antioxidant activity of reduced forms of mitochondria-targeted quinones, a novel type of geroprotectors. Aging (Albany NY), 1 (5): 481–489

    Article  CAS  Google Scholar 

  • Russell E G, Cotter T G (2015). New Insight into the Role of Reactive Oxygen Species (ROS) in Cellular Signal-Transduction Processes, 319: 221–254

    Google Scholar 

  • Sahin E, Gumuslu S (2007). Immobilization stress in rat tissues: alteration of protein oxidation, lipid peroxidation and antioxidant defense system. Comp Biochem Physio. C. Toxicol Pharmacol, 144 (4): 324–347

    Article  CAS  Google Scholar 

  • Schieber M, Chandel N S (2014). ROS function in redox signaling and oxidative stress. Curr Biol, 24(10): R453–R462

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sena L A, Chandel N S (2012). Physiological roles of mitochondrial reactive oxygen species. Mol Cell, 48(2): 158–167

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Skulachev V P (2007). A biochemical approach to the problem of aging: “megaproject” on membrane-penetrating ions. The first results and prospects. Biochemistry (Mosc), 72(12): 1385–1396

    Article  CAS  Google Scholar 

  • Skulachev V P, Anisimov V N, Antonenko Y N, Bakeeva L E, Chernyak B V, Erichev V P, Filenko O F, Kalinina N I, Kapelko V I, Kolosova N G, Kopnin B P, Korshunova G A, Lichinitser M R, Obukhova L A, Pasyukova E G, Pisarenko O I, Roginsky V A, Ruuge E K, Senin I I, Severina I I, Skulachev M V, Spivak I M, Tashlitsky V N, Tkachuk V A, Vyssokikh M Y, Yaguzhinsky L S, Zorov D B (2009). An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta, 1787(5): 437–461

    Article  PubMed  CAS  Google Scholar 

  • Steinhubl S R (2008). Why have antioxidants failed in clinical trials? Am J Cardiol, 101(1010A): 14D–19D

    Article  PubMed  CAS  Google Scholar 

  • Taverne Y J, Bogers A J, Duncker D J, Merkus D (2013). Reactive oxygen species and the cardiovascular system. Oxid Med Cell Longev, 2013: 862423

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tell G, Quadrifoglio F, Tiribelli C, Kelley M R (2009). The many functions of APE1/Ref-1: not only a DNA repair enzyme. Antioxid Redox Signal, 11(3): 601–620

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Uchida K (2000). Role of reactive aldehyde in cardiovascular diseases. Free Radic Biol Med, 28(12): 1685–1696

    Article  PubMed  CAS  Google Scholar 

  • Uchida K (2003). 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog Lipid Res, 42(4): 318–343

    Article  PubMed  CAS  Google Scholar 

  • Valko M, Izakovic M, Mazur M (2004). Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem, 266 (1–2): 37–56

    Article  PubMed  CAS  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin M T, Mazur M, Telser J (2007). Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol, 39(1): 44–84

    Article  PubMed  CAS  Google Scholar 

  • Vivekananthan D P, Penn M S, Sapp S K, Hsu A, Topol E J (2003). Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet, 361(9374): 2017–2023

    Article  PubMed  CAS  Google Scholar 

  • Wang G, Kawakami K, Gick G (2007). Regulation of Na,K-ATPase alpha1 subunit gene transcription in response to low K(+): role of CRE/ATF-and GC box-binding proteins. J Cell Physiol, 213(1): 167–176

    Article  PubMed  CAS  Google Scholar 

  • Welch K D, Davis T Z, Van Eden M E, Aust S D (2002). Deleterious iron-mediated oxidation of biomolecules. Free Radic Biol Med, 32 (7): 577–583

    Article  PubMed  CAS  Google Scholar 

  • Wilson L A, Yamamoto H, Singh G (2004). Role of the transcription factor Ets-1 in cisplatin resistance. Mol Cancer Ther, 3(7): 823–832

    PubMed  CAS  Google Scholar 

  • Winterbourn C C (2008). Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol, 4(5): 278–286

    Article  PubMed  CAS  Google Scholar 

  • Winterbourn C C (2013). The biological chemistry of hydrogen peroxide. Methods Enzymol, 528: 3–25

    Article  PubMed  CAS  Google Scholar 

  • Ye Y, Li J, Yuan Z (2013). Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. PLoS One, 8(2): e56803

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yuksel S, Asma D, Yesilada O (2008). Antioxidative and metabolic responses to extended cold exposure in rats. Acta Biol Hung, 59(1): 57–66

    Article  PubMed  Google Scholar 

  • Zablocka A, Janusz M (2008). [The two faces of reactive oxygen species]. Postepy Hig Med Dosw (Online), 62: 118–124

    Google Scholar 

  • Zhang D X, Gutterman D D (2007). Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol, 292(5): H2023–H2031

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vadim V. Davydov.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Davydov, V.V., Shestopalov, A.V. & Grabovetskaya, E.R. Physiological significance of oxidative stress and its role in adaptation of the human body to deleterious factors. Front. Biol. 13, 19–27 (2018). https://doi.org/10.1007/s11515-018-1482-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11515-018-1482-6

Keywords

Navigation