Skip to main content
SpringerLink
Log in

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

  • Otology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  7. Ohinata Y, Yamasoba T, Schacht J, Miller JM (2000) Glutathione limits noise-induced hearing loss. Hear Res 146(1–2):28–34

    Article  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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 4:358–364

    Article  CAS  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 16:2387–2392

    Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 519:87–92

    Article  CAS  Google Scholar 

  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):62–71

    Article  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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):8–10

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of ENT, Ankara Atatürk Education and Research Hospital, 06800, Ankara, Turkey

    Gülin Gökçen Kesici

  2. Department of ENT, Gülhane Education and Research Hospital, 06010, Ankara, Turkey

    Fatma Ceyda Akın Öcal

  3. Department of Histology and Embryology, Celal Bayar University, 45030, Manisa, Turkey

    Seren Gülşen Gürgen

  4. Department of Medical Pharmacology, Başkent University, 06790, Ankara, Turkey

    Şaban Remzi Erdem

  5. Department of Biostatistics, Başkent University, 06790, Ankara, Turkey

    Ersin Öğüş

  6. Department of ENT, Başkent University, 06500, Ankara, Turkey

    Hatice Seyra Erbek & Levent Naci Özlüoğlu

Authors
  1. Gülin Gökçen Kesici
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatma Ceyda Akın Öcal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seren Gülşen Gürgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Şaban Remzi Erdem
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ersin Öğüş
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hatice Seyra Erbek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Levent Naci Özlüoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gülin Gökçen Kesici.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kesici, G.G., Öcal, F.C.A., Gürgen, S.G. et al. The protective effect of metformin against the noise-induced hearing loss. Eur Arch Otorhinolaryngol 275, 2957–2966 (2018). https://doi.org/10.1007/s00405-018-5161-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-018-5161-7

Keywords

Search

Navigation