Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea

  • Seyit Mehmet CeylanEmail author
  • Erdal Uysal
  • Serdar Altinay
  • Efe Sezgin
  • Nagihan Bilal
  • Emine Petekkaya
  • Mehmet Dokur
  • Mahmut Alper Kanmaz
  • Mustafa Emre Gulbagci



The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis.


A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25 mg/kg) in which milrinone was administered 1 h before acoustic trauma (AT) and 2 h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50 mg/kg) in which the drug was administered 1 h before AT and 2 h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5 days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining.


In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5 days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001).


We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.


Milrinone Acoustic trauma Hearing loss Caspase 3 Apoptosis Inner ear 


Compliance with ethical standards

Conflict of interest

We have neither financial disclosure nor conflict of interest.

Ethical approval

The study was performed in accordance with the 2011 Guide for the Care and Use of Laboratory Animals.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology, Faculty of MedicineSanko UniversityGaziantepTurkey
  2. 2.Department of General Surgery, Faculty of MedicineSanko UniversityGaziantepTurkey
  3. 3.Department of PathologyBakırköy Dr Sadi Konuk Health Application and Research CenterIstanbulTurkey
  4. 4.Laboratory of Nutrigenomics and Epidemiology, Department of Food EngineeringIzmir Institute of ThecnologyIzmirTurkey
  5. 5.Department of Otorhinolaryngology, Faculty of MedicineKahramanmaras Sutcu Imam UniversityKahramanmarasTurkey
  6. 6.Department of Anatomy, Faculty of MedicineBeykent UniversityIstanbulTurkey
  7. 7.Department of Emergency Medicine, Faculty of MedicineBiruni UniversityIstanbulTurkey

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