The human neuroprotective placental protein composition suppressing tinnitus and restoring auditory brainstem response in a rodent model of sodium salicylate-induced ototoxicity

Mohammad Farhadi, Ali Gorji, Marjan Mirsalehi, Marcus Müller, Alexander Borisovich Poletaev, Fereidoun Mahboudi, Abdoreza Asadpour, Mohammad Ebrahimi, Mohaddeseh Beiranvand, Mohaddeseh Dehghani Khaftari, Zeinab Akbarnejad, Saeid Mahmoudian

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Abstract

The effect of neuroprotective placental protein composition (NPPC) on the suppression of tinnitus and the restoration of the auditory brainstem response (ABR) characteristics was explored in tinnitus-induced rats. The animals were placed into two groups: (1) the study group, rats received sodium salicylate (SS) at the dose of 200 mg/kg twice a day for two weeks, and then 0.4 mg of the NPPC per day, between the 14th and 28th days, (2) the placebo group, rats received saline for two weeks, and then the NPPC alone between the 14th and 28th days. The gap pre-pulse inhibition of the acoustic startle (GPIAS), the pre-pulse inhibition (PPI), and the ABR assessments were performed on animals in both groups three times (baseline, day 14, and 28). The GPIAS value declined after 14 consecutive days of the SS injection, while NPPC treatment augmented the GPIAS score in the study group on the 28th day. The PPI outcomes revealed no significant changes, indicating hearing preservation after the SS and NPPC administrations. Moreover, some changes in ABR characteristics were observed following SS injection, including (1) higher ABR thresholds, (2) lowered waves I and II amplitudes at the frequencies of 6, 12, and 24 kHz and wave III at the 12 kHz, (3) elevated amplitude ratios, and (4) prolongation in brainstem transmission time (BTT). All the mentioned variables returned to their normal values after applying the NPPC. The NPPC use could exert positive therapeutic effects on the tinnitus-induced rats and improve their ABR parameters.
Original languageEnglish
Article numbere19052
Pages (from-to)1-18
Number of pages18
JournalHeliyon
Volume9
Issue number8
Early online date11 Aug 2023
DOIs
Publication statusPublished online - 11 Aug 2023

Bibliographical note

Funding Information:
The support of the Iran National Science Foundation (INSF), ENT and Head & Neck Research Center, Iran University of Medical Sciences to assign credit to the research line auditory neuroscience is gratefully acknowledged. Also, all authors would like to appreciate the late Professor Alexander Borisovich Poletaev (*06 November 1951 – † March 6th, 2021). He was the first to report the evident positive effects of the protein fraction of porcine placental extract introduced by Alexander Anikin, in terms of having prominent neuroprotective properties, initially named X-proteins (XP). He also generously provided the placenta extract extraction method to this research group. Moreover, the authors would like to extend special thanks to Professor Marcus Müller (*06 November 1957 – †14 June 2020), Associate Professor of Physiology, Department of Otolaryngology, Head, and Neck Surgery of the University of Tübingen, Tübingen, Germany, for his unwavering support to set up the ABR system and record appropriate waveforms. He was a highly recognized auditory physiologist, tireless researcher, and dedicated teacher. The authors further thank all colleagues as well as administrative personnel at Shefa Neuroscience Institute, Tehran, Iran, who contributed to data collection.

Funding Information:
This study was financially supported by the Iran National Science Foundation (INSF, Synergy Grant Code no. insf-98020383-1400/03/23), and ENT and Head & Neck Research Center, Hazrate Rasoul Akram Hospital, the Five Senses Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran (Ethical approval no. IR.IUMS.REC.1398.233).The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Mohammad Farhadi reports financial support was provided by Iran National Science Foundation. Dr. Saeid Mahmoudian reports financial support and administrative support were provided by ENT and Head and Neck Research Center, The Five Senses Health Institute, Iran University of Medical Sciences.

Funding Information:
This study was financially supported by the Iran National Science Foundation (INSF, Synergy Grant Code no. insf-98020383-1400/03/23 ), and ENT and Head & Neck Research Center, Hazrate Rasoul Akram Hospital, the Five Senses Institute, School of Medicine, Iran University of Medical Sciences , Tehran, Iran (Ethical approval no. IR.IUMS.REC.1398.233 ).

Publisher Copyright:
© 2023

Keywords

  • Tinnitus
  • Evoked potentials
  • Auditory
  • Auditory brain stem response
  • Placental extract

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