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Free Radicals and Oxidative Stress: Basic Concepts and Misconceptions

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Book cover Free Radicals in ENT Pathology

Abstract

Free radicals have been shown to be involved in various ENT pathology conditions. While it is widely recognized that excessive amounts free radicals, including reactive oxygen species (ROSs) and reactive nitrogen species (RNSs), can be harmful and damage cell structures, in strong contrast, at low concentrations they can act as cellular and intracellular signaling molecules that facilitate normal biological processes. Current understanding of the involvement of free radicals in pathology suggests that antioxidant therapy through attenuating free radicals may be important to optimize treatment. Some studies in animal models and human subjects, however, have been less conclusive. This raises the concern that the complexities of free-radical biology and antioxidant treatments as well as practical variations of human participants may make it impossible to study single effects of antioxidant compounds. Physical exercise and a healthy diet that includes a high intake of natural complex antioxidant mixtures, for example, may influence the effects of antioxidant supplementation. Moreover, antioxidants are vulnerable to rapid changes in oxygenation (ischemia/reperfusion), light, temperature, and, most importantly, redox-active transition metals, which could act as prooxidants under certain conditions, both in vitro and in vivo.

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Abbreviations

8-oxodGuo:

8-Oxo-7,8-dihydro-2′-deoxyguanosine

8-oxoGuo:

8-Oxo-7,8-dihydro-guanosine

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

EC:

Epicatechin

ECG:

Epicatechin gallate

EGC:

Epigallocatechin

EGCG:

Epigallocatechin gallate

ELISA:

Enzyme-linked immunosorbent assay

ESR:

Electron spin resonance

GC/MS:

Gas chromatography-mass spectrometry

GPX:

Glutathione peroxidase

HPLC:

High-performance liquid chromatography

MDA:

Malondialdehyde

NADP:

Nicotinamide adenine dinucleotide phosphate

RNSs:

Reactive nitrogen species

ROSs:

Reactive oxygen species

SODs:

Superoxide dismutases

TBAR:

Thiobarbituric acid reactive substances

References

  • Aksoy F, Demirhan H, Veyseller B, Yildirim YS, Ozturan O, Basinoglu F (2009) Advanced oxidation protein products as an oxidative stress marker in allergic rhinitis. Kulak Burun Bogaz Ihtis Derg 19(6):279–284

    PubMed  Google Scholar 

  • Aksoy F, Yildirim YS, Veyseller B, Demirhan H, Ozturan O (2012) Serum levels of advanced oxidation protein products in response to allergen exposure in allergic rhinitis. Ear Nose Throat J 91(8):E32–E35

    PubMed  Google Scholar 

  • Baysal E, Aksoy N, Kara F, Taysi S, Taskin A, Bilinc H, Cevik C, Celenk F, Kanlikama M (2013) Oxidative stress in chronic otitis media. Eur Arch Otorhinolaryngol 270(4):1203–1208. doi:10.1007/s00405-012-2070-z

    Article  PubMed  Google Scholar 

  • Bienert GP, Chaumont F (2014) Aquaporin-facilitated transmembrane diffusion of hydrogen peroxide. Biochim Biophys Acta 1840(5):1596–1604. doi:10.1016/j.bbagen.2013.09.017

    Article  CAS  PubMed  Google Scholar 

  • Bonabi S, Caelers A, Monge A, Huber A, Bodmer D (2008) Resveratrol protects auditory hair cells from gentamicin toxicity. Ear Nose Throat J 87(10):570–573

    PubMed  Google Scholar 

  • Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134(3):707–716

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boveris A, Cadenas E, Stoppani AO (1976) Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochem J 156(2):435–444

    CAS  PubMed Central  PubMed  Google Scholar 

  • Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  CAS  PubMed  Google Scholar 

  • Buetler TM, Krauskopf A, Ruegg UT (2004) Role of superoxide as a signaling molecule. News Physiol Sci 19:120–123

    CAS  PubMed  Google Scholar 

  • Cabantchik ZI, Kakhlon O, Epsztejn S, Zanninelli G, Breuer W (2002) Intracellular and extracellular labile iron pools. Adv Exp Med Biol 509:55–75

    Article  CAS  PubMed  Google Scholar 

  • Cantu D, Schaack J, Patel M (2009) Oxidative inactivation of mitochondrial aconitase results in iron and H2O2-mediated neurotoxicity in rat primary mesencephalic cultures. PLoS One 4(9):e7095

    Article  PubMed Central  PubMed  Google Scholar 

  • Cemek M, Dede S, Bayiroglu F, Caksen H, Cemek F, Yuca K (2005) Oxidant and antioxidant levels in children with acute otitis media and tonsillitis: a comparative study. Int J Pediatr Otorhinolaryngol 69(6):823–827

    Article  PubMed  Google Scholar 

  • Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59(3):527–605

    CAS  PubMed  Google Scholar 

  • Citardi MJ, Song W, Batra PS, Lanza DC, Hazen SL (2006) Characterization of oxidative pathways in chronic rhinosinusitis and sinonasal polyposis. Am J Rhinol 20(3):353–359

    Article  PubMed  Google Scholar 

  • Cvetkovic T, Vlahovic P, Todorovic M, Stankovic M (2009) Investigation of oxidative stress in patients with chronic tonsillitis. Auris Nasus Larynx 36(3):340–344

    Article  PubMed  Google Scholar 

  • Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329(1–2):23–38

    Article  CAS  PubMed  Google Scholar 

  • Davies KJ, Quintanilha AT, Brooks GA, Packer L (1982) Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 107(4):1198–1205

    Article  CAS  PubMed  Google Scholar 

  • Ding D, Qi W, Yu D, Jiang H, Han C, Kim MJ, Katsuno K, Hsieh YH, Miyakawa T, Salvi R, Tanokura M, Someya S (2013) Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures. PLoS One 8(11):e79817

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dwivedi R, Raturi D, Kandpal N, Singh R, Puri V (2008) Oxidative stress in patients with laryngeal carcinoma. Indian J Cancer 45(3):97–99

    Article  PubMed  Google Scholar 

  • Fetoni AR, Piacentini R, Fiorita A, Paludetti G, Troiani D (2009) Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL). Brain Res 1257:108–116

    Article  CAS  PubMed  Google Scholar 

  • Fetoni AR, Troiani D, Eramo SL, Rolesi R, Paludetti Troiani G (2012) Efficacy of different routes of administration for Coenzyme Q10 formulation in noise-induced hearing loss: systemic versus transtympanic modality. Acta Otolaryngol 132(4):391–399

    Article  CAS  PubMed  Google Scholar 

  • Furukawa A, Oikawa S, Murata M, Hiraku Y, Kawanishi S (2003) (-)-Epigallocatechin gallate causes oxidative damage to isolated and cellular DNA. Biochem Pharmacol 66(9):1769–1778

    Article  CAS  PubMed  Google Scholar 

  • Furukawa-Hibi Y, Yoshida-Araki K, Ohta T, Ikeda K, Motoyama N (2002) FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress. J Biol Chem 277(30):26729–26732

    Article  CAS  PubMed  Google Scholar 

  • Garca MF, Aslan M, Tuna B, Kozan A, Cankaya H (2013a) Serum myeloperoxidase activity, total antioxidant capacity and nitric oxide levels in patients with chronic otitis media. J Membr Biol 246(7):519–524

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Garca MF, Demir H, Turan M, Bozan N, Kozan A, Belli SB, Arslan A, Cankaya H (2013b) Assessment of adenosine deaminase (ADA) activity and oxidative stress in patients with chronic tonsillitis. Eur Arch Otorhinolaryngol. doi:10.1007/s00405-013-2843-z

    PubMed  Google Scholar 

  • Giulivi C, Poderoso JJ, Boveris A (1998) Production of nitric oxide by mitochondria. J Biol Chem 273(18):11038–11043

    Article  CAS  PubMed  Google Scholar 

  • Gopinath B, Schneider J, Flood VM, McMahon CM, Burlutsky G, Leeder SR, Mitchell P (2014) Association between diet quality with concurrent vision and hearing impairment in older adults. J Nutr Health Aging 18(3):251–256

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JM (1992) Biologically relevant metal ion-dependent hydroxyl radical generation. An update. FEBS Lett 307(1):108–112

    Article  CAS  PubMed  Google Scholar 

  • Hofer T, Seo AY, Prudencio M, Leeuwenburgh C (2006) A method to determine RNA and DNA oxidation simultaneously by HPLC-ECD: greater RNA than DNA oxidation in rat liver after doxorubicin administration. Biol Chem 387(1):103–111

    Article  CAS  PubMed  Google Scholar 

  • Kakhlon O, Cabantchik ZI (2002) The labile iron pool: characterization, measurement, and participation in cellular processes(1). Free Radic Biol Med 33(8):1037–1046

    Article  CAS  PubMed  Google Scholar 

  • Koskenkorva-Frank TS, Weiss G, Koppenol WH, Burckhardt S (2013) The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: Insights into the potential of various iron therapies to induce oxidative and nitrosative stress. Free Radic Biol Med 65:1174–1194

    Article  CAS  PubMed  Google Scholar 

  • Kozlov AV, Yegorov DY, Vladimirov YA, Azizova OA (1992) Intracellular free iron in liver tissue and liver homogenate: studies with electron paramagnetic resonance on the formation of paramagnetic complexes with desferal and nitric oxide. Free Radic Biol Med 13(1):9–16

    Article  CAS  PubMed  Google Scholar 

  • Lai MT, Ohmichi T, Ogawa T, Nishizaki K, Masuda Y (1997) Electron spin resonance spin trapping assay and immunohistochemical localization of superoxide dismutases in the rat nasal mucosa. Acta Otolaryngol 117(3):437–446

    Article  CAS  PubMed  Google Scholar 

  • Leeuwenburgh C, Heinecke JW (2001) Oxidative stress and antioxidants in exercise. Curr Med Chem 8(7):829–838

    Article  CAS  PubMed  Google Scholar 

  • Li XL, Zhou AG, Zhang L, Chen WJ (2011) Antioxidant status and immune activity of glycyrrhizin in allergic rhinitis mice. Int J Mol Sci 12(2):905–916

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lu J, Li W, Du X, Ewert DL, West MB, Stewart C, Floyd RA, Kopke RD (2014) Antioxidants reduce cellular and functional changes induced by intense noise in the inner Ear and cochlear nucleus. J Assoc Res Otolaryngol. doi:10.1007/s10162-014-0441-4

    PubMed  Google Scholar 

  • Manjunath MK, Annam V, Suresh DR (2010) Significance of free radical injury in laryngeal and hypopharyngeal cancers. J Laryngol Otol 124(3):315–317

    Article  CAS  PubMed  Google Scholar 

  • Mendelsohn AR, Larrick JW (2013) Trade-offs between anti-aging dietary supplementation and exercise. Rejuvenation Res 16(5):419–426

    Article  CAS  PubMed  Google Scholar 

  • Morrow JD, Roberts LJ (1997) The isoprostanes: unique bioactive products of lipid peroxidation. Prog Lipid Res 36(1):1–21

    Article  CAS  PubMed  Google Scholar 

  • Oikawa S, Furukawaa A, Asada H, Hirakawa K, Kawanishi S (2003) Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species. Free Radic Res 37(8):881–890

    Article  CAS  PubMed  Google Scholar 

  • Petrat F, de Groot H, Sustmann R, Rauen U (2002) The chelatable iron pool in living cells: a methodically defined quantity. Biol Chem 383(3–4):489–502

    CAS  PubMed  Google Scholar 

  • Pollack M, Leeuwenburgh C (1999) Molecular mechanisms of oxidative stress in aging: free radicals, aging, antioxidants and disease. In: Sen CK, Packer L, Hannien O (eds) Handbook of Oxidants and Antioxidants in Exercise. Elsevier Science, Amsterdam

    Google Scholar 

  • Rauen U, Springer A, Weisheit D, Petrat F, Korth HG, de Groot H, Sustmann R (2007) Assessment of chelatable mitochondrial iron by using mitochondrion-selective fluorescent iron indicators with different iron-binding affinities. Chembiochem 8(3):341–352

    Article  CAS  PubMed  Google Scholar 

  • Rewerska A, Pawelczyk M, Rajkowska E, Politanski P, Sliwinska-Kowalska M (2013) Evaluating D-methionine dose to attenuate oxidative stress-mediated hearing loss following overexposure to noise. Eur Arch Otorhinolaryngol 270(4):1513–1520

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rothman RJ, Serroni A, Farber JL (1992) Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin, that is involved in oxidative cell injury. Mol Pharmacol 42(4):703–710

    CAS  PubMed  Google Scholar 

  • Sataloff RT, Bittermann T, Marks L, Lurie D, Hawkshaw M (2010) The effects of glutathione enhancement on sensorineural hearing loss. Ear Nose Throat J 89(9):422–433

    PubMed  Google Scholar 

  • Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6(4):280–293

    Article  CAS  PubMed  Google Scholar 

  • Seidman MD, Tang W, Bai VU, Ahmad N, Jiang H, Media J, Patel N, Rubin CJ, Standring RT (2013) Resveratrol decreases noise-induced cyclooxygenase-2 expression in the rat cochlea. Otolaryngol Head Neck Surg 148(5):827–833

    Article  PubMed  Google Scholar 

  • Shargorodsky J, Curhan SG, Eavey R, Curhan GC (2010) A prospective study of vitamin intake and the risk of hearing loss in men. Otolaryngol Head Neck Surg 142(2):231–236

    Article  PubMed Central  PubMed  Google Scholar 

  • Sohal RS, Wennberg-Kirch E, Jaiswal K, Kwong LK, Forster MJ (1999) Effect of age and caloric restriction on bleomycin-chelatable and nonheme iron in different tissues of C57BL/6 mice. Free Radic Biol Med 27(3–4):287–293

    Article  CAS  PubMed  Google Scholar 

  • Someya S, Tanokura M, Weindruch R, Prolla TA, Yamasoba T (2010) Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. Curr Aging Sci 3(1):20–25

    Article  PubMed Central  PubMed  Google Scholar 

  • Suh KS, Chon S, Oh S, Kim SW, Kim JW, Kim YS, Woo JT (2010) Prooxidative effects of green tea polyphenol (-)-epigallocatechin-3-gallate on the HIT-T15 pancreatic beta cell line. Cell Biol Toxicol 26(3):189–199

    Article  CAS  PubMed  Google Scholar 

  • Testa D, Guerra G, Marcuccio G, Landolfo PG, Motta G (2012) Oxidative stress in chronic otitis media with effusion. Acta Otolaryngol 132(8):834–837

    CAS  PubMed  Google Scholar 

  • Tian G, Sawashita J, Kubo H, Nishio SY, Hashimoto S, Suzuki N, Yoshimura H, Tsuruoka M, Wang Y, Liu Y, Luo H, Xu Z, Mori M, Kitano M, Hosoe K, Takeda T, Usami SI, Higuchi K (2013) Ubiquinol-10 supplementation activates mitochondria functions to decelerate senescence in senescence-accelerated mice. Antioxid Redox Signal. doi:10.1089/ars.2013.5406

    Google Scholar 

  • Uslu C, Taysi S, Bakan N (2003) Lipid peroxidation and antioxidant enzyme activities in experimental maxillary sinusitis. Ann Clin Lab Sci 33(1):18–22

    CAS  PubMed  Google Scholar 

  • Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160(1):1–40

    Article  CAS  PubMed  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, 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  CAS  PubMed  Google Scholar 

  • Xiong M, He Q, Lai H, Huang W, Wang L, Yang C (2012) Radix astragali injection enhances recovery from sudden deafness. Am J Otolaryngol 33(5):523–527

    Article  PubMed  Google Scholar 

  • Xu J, Knutson MD, Carter CS, Leeuwenburgh C (2008) Iron accumulation with age, oxidative stress and functional decline. PLoS One 3(8):e2865

    Article  PubMed Central  PubMed  Google Scholar 

  • Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K (2013) Current concepts in age-related hearing loss: epidemiology and mechanistic pathways. Hear Res 303:30–38

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yilmaz T, Kocan EG, Besler HT (2004) The role of oxidants and antioxidants in chronic tonsillitis and adenoid hypertrophy in children. Int J Pediatr Otorhinolaryngol 68(8):1053–1058

    Article  PubMed  Google Scholar 

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Correspondence to Jinze Xu .

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Xu, J., Leeuwenburgh, C. (2015). Free Radicals and Oxidative Stress: Basic Concepts and Misconceptions. In: Miller, J., Le Prell, C., Rybak, L. (eds) Free Radicals in ENT Pathology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-13473-4_2

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