Abstract
The aim of this study was to investigate the 4977 and 7400 bp deletions of mitochondrial DNA in patients with chronic suppurative otitis media and to indicate the possible association of mitochondrial DNA deletions with chronic suppurative otitis media. Thirty-six patients with chronic suppurative otitis media were randomly selected to assess the mitochondrial DNA deletions. Tympanomastoidectomy was applied for the treatment of chronic suppurative otitis media, and the curettage materials including middle ear tissues were collected. The 4977 and 7400 bp deletion regions and two control regions of mitochondrial DNA were assessed by using the four pair primers. DNA was extracted from middle ear tissues and peripheral blood samples of the patients, and then polymerase chain reactions (PCRs) were performed. PCR products were separated in 2 % agarose gel. Seventeen of 36 patients had the heterozygote 4977 bp deletion in the middle ear tissue but not in peripheral blood. There wasn’t any patient who had the 7400 bp deletion in mtDNA of their middle ear tissue or peripheral blood tissue. The patients with the 4977 bp deletion had a longer duration of chronic suppurative otitis media and a higher level of hearing loss than the others (p < 0.01). Long time chronic suppurative otitis media and the reactive oxygen species can cause the mitochondrial DNA deletions and this may be a predisposing factor to sensorineural hearing loss in chronic suppurative otitis media. An antioxidant drug as a scavenger agent may be used in long-term chronic suppurative otitis media.
Similar content being viewed by others
References
Bluestone CD (1998) Epidemiology and pathogenesis of chronic suppurative otitis media: implications for prevention and treatment. Int J Pediatr Otorhinolaryngol 42:207–223
Chapple IL (1997) Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol 24:287–296
Freitas M, Lima JL, Fernandes E (2009) Optical probes for detection and quantification of neutrophils’oxidative burst. A review. Anal Chim Acta 649:8–23
Poyton RO, Ball KA, Castello PR (2009) Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab 20:332–340
Kim HR, Won SJ, Fabian C, Kang MG, Szardenings M, Shin MG (2015) Mitochondrial DNA aberrations and pathophysiological implications in hematopoietic diseases, chronic inflammatory diseases, and cancers. Ann Lab Med 35:1–14
Henderson D, Bielefeld EC, Harris KC, Hu BH (2006) The role of oxidative stress in noise-induced hearing loss. Ear Hear 27:1–19
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
Oliveira PH, da Silva CL, Cabral JM (2013) An appraisal of human mitochondrial DNA instability: new insights into the role of non-canonical DNA structures and sequence motifs. PLoS One 8:e59907
Peng TI, Yu PR, Chen JY, Wang HL, Wu HY, Wei YH, Jou MJ (2006) Visualizing common deletion of mitochondrial DNA-augmented mitochondrial reactive oxygen species generation and apoptosis upon oxidative stress. Biochim Biophys Acta 1762:241–255
Hattori K, Tanaka M, Sugiyama S, Obayashi T, Ito T, Satake T, Hanaki Y, Asai J, Nagano M, Ozawa T (1991) Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor to presbycardia. Am Heart J 121:1735–1742
Markaryan A, Nelson EG, Hinojosa R (2008) Detection of mitochondrial DNA deletions in the cochlea and its structural elements from archival human temporal bone tissue. Mutat Res 640:38–45
Vivero RJ, Ouyang X, Yan D, Du L, Liu W, Angeli SI, Liu XZ (2012) Mitochondrial DNA mutation screening in an ethnically diverse nonsyndromic deafness cohort. Genet Test Mol Biomark 16:1146–1148
Fischel-Ghodsian N (1999) Mitochondrial deafness mutations reviewed. Hum Mutat 13:261–270
Yelverton JC, Arnos K, Xia XJ, Nance WE, Pandya A, Dodson KM (2013) The clinical and audiologic features of hearing loss due to mitochondrial mutations. Otolaryngol Head Neck Surg 148:1017–1022
Ouyang XM, Yan D, Yuan HJ, Pu D, Du LL, Han DY, Liu XZ (2009) The genetic bases for non-syndromic hearing loss among Chinese. J Hum Genet 54:131–140
Chinnery PF, Elliott C, Green GR, Rees A, Coulthard A, Turnbull DM, Griffiths TD (2000) The spectrum of hearing loss due to mitochondrial DNA defects. Brain 123(Pt 1):82–92
Ueda N, Oshima T, Ikeda K, Abe K, Aoki M, Takasaka T (1998) Mitochondrial DNA deletion is a predisposing cause for sensorineural hearing loss. Laryngoscope 108:580–584
Bai U, Seidman MD (2001) A specific mitochondrial DNA deletion (mtDNA4977) is identified in a pedigree of a family with hearing loss. Hear Res 154:73–80
Kokotas H, Petersen MB, Willems PJ (2007) Mitochondrial deafness. Clin Genet 71:379–391
Gold M, Rapin I (1994) Non-Mendelian mitochondrial inheritance as a cause of progressive genetic sensorineural hearing loss. Int J Pediatr Otorhinolaryngol 30:91–104
Fischel-Ghodsian N (2005) Genetic factors in aminoglycoside toxicity. Pharmacogenomics 6:27–36
Rotig A, Cormier V, Blanche S, Bonnefont JP, Ledeist F, Romero N, Schmitz J, Rustin P, Fischer A, Saudubray JM et al (1990) Pearson’s marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest 86:1601–1608
Nie H, Shu H, Vartak R, Milstein AC, Mo Y, Hu X, Fang H, Shen L, Ding Z, Lu J, Bai Y (2013) Mitochondrial common deletion, a potential biomarker for cancer occurrence, is selected against in cancer background: a meta-analysis of 38 studies. PLoS One 8:e67953
Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, Beal MF, Wallace DC (1992) Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat Genet 2:324–329
Canakci CF, Tatar A, Canakci V, Cicek Y, Oztas S, Orbak R (2006) New evidence of premature oxidative DNA damage: mitochondrial DNA deletion in gingival tissue of patients with periodontitis. J Periodontol 77:1894–1900
Taylor SD, Ericson NG, Burton JN, Prolla TA, Silber JR, Shendure J, Bielas JH (2014) Targeted enrichment and high-resolution digital profiling of mitochondrial DNA deletions in human brain. Aging Cell 13:29–38
Canakci CF, Canakci V, Tatar A, Eltas A, Sezer U, Cicek Y, Oztas S (2009) Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis. Arch Immunol Ther Exp (Warsz) 57:205–211
Prince LR, Bianchi SM, Vaughan KM, Bewley MA, Marriott HM, Walmsley SR, Taylor GW, Buttle DJ, Sabroe I, Dockrell DH, Whyte MK (2008) Subversion of a lysosomal pathway regulating neutrophil apoptosis by a major bacterial toxin, pyocyanin. J Immunol 180:3502–3511
Sedo-Cabezon L, Boadas-Vaello P, Soler-Martin C, Llorens J (2014) Vestibular damage in chronic ototoxicity: a mini-review. Neurotoxicology 43:21–27
Bravo O, Ballana E, Estivill X (2006) Cochlear alterations in deaf and unaffected subjects carrying the deafness-associated A1555G mutation in the mitochondrial 12S rRNA gene. Biochem Biophys Res Commun 344:511–516
Zhong Y, Hu YJ, Yang Y, Peng W, Sun Y, Chen B, Huang X, Kong WJ (2011) Contribution of common deletion to total deletion burden in mitochondrial DNA from inner ear of d-galactose-induced aging rats. Mutat Res 712:11–19
Menardo J, Tang Y, Ladrech S, Lenoir M, Casas F, Michel C, Bourien J, Ruel J, Rebillard G, Maurice T, Puel JL, Wang J (2012) Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea. Antioxid Redox Signal 16:263–274
Khaĭmanova IuV, Kosiakov SIa (2012) [The influence of chronic otitis media on the sensorineural component of hearing]. Vestn Otorinolaringol (3):7–10
Garca MF, Aslan M, Tuna B, Kozan A, Cankaya H (2013) Serum myeloperoxidase activity, total antioxidant capacity and nitric oxide levels in patients with chronic otitis media. J Membr Biol 246:519–524
Seidman MD (2000) Effects of dietary restriction and antioxidants on presbyacusis. Laryngoscope 110:727–738
Heman-Ackah SE, Juhn SK, Huang TC, Wiedmann TS (2010) A combination antioxidant therapy prevents age-related hearing loss in C57BL/6 mice. Otolaryngol Head Neck Surg 143:429–434
Mukherjea D, Rybak LP, Sheehan KE, Kaur T, Ramkumar V, Jajoo S, Sheth S (2011) The design and screening of drugs to prevent acquired sensorineural hearing loss. Expert Opin Drug Discov 6:491–505
Polony G, Humli V, Ando R, Aller M, Horvath T, Harnos A, Tamas L, Vizi ES, Zelles T (2014) Protective effect of rasagiline in aminoglycoside ototoxicity. Neuroscience 265:263–273
Acknowledgments
We thank Prof. Hasan Turkez, PhD, from Erzurum Technical University, for statistical analysis of this study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Tatar, A., Tasdemir, S., Sahin, I. et al. Mitochondrial DNA deletions in patients with chronic suppurative otitis media. Eur Arch Otorhinolaryngol 273, 2473–2479 (2016). https://doi.org/10.1007/s00405-015-3839-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00405-015-3839-7