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The protective effect of metformin against the noise-induced hearing loss

  • Gülin Gökçen Kesici
  • Fatma Ceyda Akın Öcal
  • Seren Gülşen Gürgen
  • Şaban Remzi Erdem
  • Ersin Öğüş
  • Hatice Seyra Erbek
  • Levent Naci Özlüoğlu
Otology
  • 29 Downloads

Abstract

Objective

To test the protective effect of metformin against noise-induced hearing loss.

Methods

24 rats were included in the study. The first group was exposed to noise only, the second group took metformin, the third group was exposed to noise and took metformin, and the fourth group was neither exposed to noise nor took metformin as control group. After measurement of baseline DPOAE and ABR of rats, the metformin group and the metformin + noise group received 300 mg/kg/day metformin via gavage for 10 days. On the 11th day, group 1 and group 3 were exposured to white noise at 105 dB SPL for 15 h. After noise exposure, DPOAE and ABR measurements of all rats were repeated on days 1st, 7th, and 21st. At the end of the study, all animals were sacrificed and cochlear tissues were separated for immunohistochemical assessments.

Results

ABR threshold values and DPAOE measurements of groups 1 and 3 were deteriorated on the 1st day after noise, while deterioration in group 1 continued on 7th and 21st days, but normalized on 7th day in group 3. After immune staining, a significant immunoreaction was observed in the noise group, while the reaction in the noise + metformin group was close to the control group.

Conclusion

Metformin has a protective effect on noise-induced hearing loss in rats. As a conclusion, it is determined that metformin protects from permanent threshold shift in rats. It can be considered a good alternative for protecting noise-induced hearing loss.

Keywords

Noise Noise-induced hearing loss Acoustic trauma Metformin 

Notes

Acknowledgements

This study was approved by the Medical and Health Sciences Research Council of our university (Project number: DA16/26).

Funding

There is no financial support used for this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed in the study. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This study was approved by the institutional ethics committee.

References

  1. 1.
    Nelson DI, Nelson RY, Concha-Barrientos M, Fingerhut M (2005) The global burden of occupational noise-induced hearing loss. Am J Ind Med 6:446–458.  https://doi.org/10.1002/ajim.20223 CrossRefGoogle Scholar
  2. 2.
    Bielefeld EC (2013) Reduction in impulse noise-induced permanent threshold shift with intracochlear application of an NADPH oxidase inhibitor. J Am Acad Audiol 6:461–473.  https://doi.org/10.3766/jaaa.24.6.3 CrossRefGoogle Scholar
  3. 3.
    Le Prell CG, Yamashita D, Minami SB, Yamasoba T, Miller JM (2007) Mechanisms of noise-induced hearing loss indicate multiple methods of prevention. Hear Res 1:22–43.  https://doi.org/10.1016/j.heares.2006.10.006 CrossRefGoogle Scholar
  4. 4.
    Alhaider AA, Korashy HM, Sayed-Ahmed MM, Mobark M, Kfoury H, Mansour MA (2011) Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact 3:233–242.  https://doi.org/10.1016/j.cbi.2011.03.014 CrossRefGoogle Scholar
  5. 5.
    Morales AI, Detaille D, Prieto M, Puente A, Briones E, Arevalo M et al (2010) Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney Int 10:861–869.  https://doi.org/10.1038/ki.2010.11 CrossRefGoogle Scholar
  6. 6.
    Patil SP, Jain PD, Ghumatkar PJ, Tambe R, Sathaye S (2014) Neuroprotective effect of metformin in MPTP-induced Parkinson’s disease in mice. Neuroscience 277:747–754.  https://doi.org/10.1016/j.neuroscience.2014.07.046 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ohinata Y, Yamasoba T, Schacht J, Miller JM (2000) Glutathione limits noise-induced hearing loss. Hear Res 146(1–2):28–34CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Chang J, Jung HH, Yang JY, Lee S, Choi J, Im GJ, Chae SW (2014) Protective effect of metformin against cisplatin-induced ototoxicity in an auditory cell line. J Assoc Res Otolaryngol 15(2):149–158.  https://doi.org/10.1007/s10162-013-0431-y CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mao-Ying QL, Kavelaars A, Krukowski K, Huo XJ, Zhou W, Price TJ et al (2014) The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model. PLoS One 6:e100701.  https://doi.org/10.1371/journal.pone.0100701 CrossRefGoogle Scholar
  10. 10.
    Correia S, Carvalho C, Santos MS, Proença T, Nunes E, Duarte AI et al (2008) Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. Med Chem 4:358–364CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Lv WS, Wen JP, Li L, Sun RX, Wang J, Xian YX et al (2012) The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats. Brain Res 1444:11–19.  https://doi.org/10.1016/j.brainres.2012.01.028 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Abd-Elsameea AA, Moustaf AA, Mohamed AM (2014) Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/reperfusion. Eur Rev Med Pharmacol Sci 16:2387–2392Google Scholar
  13. 13.
    Oishi N, Kendall A, Schacht J (2014) Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo. Neurosci Lett 583:65–69.  https://doi.org/10.1016/j.neulet.2014.09.028 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lee JY, Lee SH, Chang JW, Song JJ, Jung HH, Im GJ (2014) Protective effect of metformin on gentamicin-induced vestibulotoxicity in rat primary cell culture. Clin Exp Otorhinolaryngol 7(4):286–294.  https://doi.org/10.3342/ceo.2014.7.4.286 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Chang J, Jung HH, Yang JY, Choi J, Im GJ, Chae SW (2011) Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line. Hear Res 282(1–2):92–96.  https://doi.org/10.1016/j.heares.2011.09.005 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Guigas B, Detaille D, Chauvin C, Batandier C, De Oliveira F, Fontaine E, Leverve X (2004) Metformin inhibits mitochondrial permeability transition and cell death: a pharmacological in vitro study. Biochem J 382(Pt 3):877–884.  https://doi.org/10.1042/BJ20040885 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lablanche S, Cottet-Rousselle C, Lamarche F, Benhamou PY, Halimi S, Leverve X, Fontaine E (2011) Protection of pancreatic INS-1 beta-cells from glucose- and fructose-induced cell death by inhibiting mitochondrial permeability transition with cyclosporin A or metformin. Cell Death Dis 2:e134.  https://doi.org/10.1038/cddis.2011.15 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Algire C, Moiseeva O, Deschenes-Simard X, Amrein L, Petruccelli L, Birman E et al (2012) Metformin reduces endogenous reactive oxygen species and associated DNA damage. Cancer Prev Res (Phila) 5(4):536–543.  https://doi.org/10.1158/1940-6207.CAPR-11-0536 CrossRefGoogle Scholar
  19. 19.
    Foller M, Jaumann M, Dettling J, Saxena A, Pakladok T, Munoz T et al (2012) AMP-activated protein kinase in BK-channel regulation and protection against hearing loss following acoustic overstimulation. FASEB J 26(10):4243–4253.  https://doi.org/10.1096/fj.12-208132 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Poels J, Spasic MR, Callaerts P, Norga KK (2009) Expanding roles for AMP-activated protein kinase in neuronal survival and autophagy. Bioessays 31(9):944–952.  https://doi.org/10.1002/bies.200900003 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Yamane H, Nakai Y, Takayama M, Konishi K, Iguchi H, Nakagawa T et al (1995) The emergence of free radicals after acoustic trauma and strial blood flow. Acta Otolaryngol Suppl 519:87–92CrossRefPubMedCentralGoogle Scholar
  22. 22.
    Hu BH, Henderson D, Nicotera TM (2002) Involvement of apoptosis in progression of cochlear lesion following exposure to intense noise. Hear Res 166(1–2):62–71CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kurabi A, Keithley EM, Housley GD, Ryan AF, Wong AC (2017) Cellular mechanisms of noise-induced hearing loss. Hear Res 349:129–137.  https://doi.org/10.1016/j.heares.2016.11.013 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Yang S, Cai Q, Bard J, Jamison J, Wang J, Yang W, Hu BH (2015) Variation analysis of transcriptome changes reveals cochlear genes and their associated functions in cochlear susceptibility to acoustic overstimulation. Hear Res 330:78–89.  https://doi.org/10.1016/j.heares.2015.04.010 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Mujica-Mota MA, Salehi P, Devic S, Daniel SJ (2014) Safety and otoprotection of metformin in radiation-induced sensorineural hearing loss in the guinea pig. Otolaryngol Head Neck Surg 150(5):859–865.  https://doi.org/10.1177/0194599814521013 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Keats BJ, Nouri N, Huang JM, Money M, Webster DB, Berlin CI (1995) The deafness locus (dn) maps to mouse chromosome 19. Mamm Genome 6(1):8–10CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Gülin Gökçen Kesici
    • 1
  • Fatma Ceyda Akın Öcal
    • 2
  • Seren Gülşen Gürgen
    • 3
  • Şaban Remzi Erdem
    • 4
  • Ersin Öğüş
    • 5
  • Hatice Seyra Erbek
    • 6
  • Levent Naci Özlüoğlu
    • 6
  1. 1.Department of ENTAnkara Atatürk Education and Research HospitalAnkaraTurkey
  2. 2.Department of ENTGülhane Education and Research HospitalAnkaraTurkey
  3. 3.Department of Histology and EmbryologyCelal Bayar UniversityManisaTurkey
  4. 4.Department of Medical PharmacologyBaşkent UniversityAnkaraTurkey
  5. 5.Department of BiostatisticsBaşkent UniversityAnkaraTurkey
  6. 6.Department of ENTBaşkent UniversityAnkaraTurkey

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