Molecular aspects of melatonin treatment in tinnitus: A review

Azam Hosseinzadeh, Seyed Kamran Kamrava, Brian C.J. Moore, Russel J. Reiter, Habib Ghaznavi, Mahboobeh Kamali, Saeed Mehrzadi

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations


Tinnitus is a hearing disorder characterized by the perception of sound without external acoustic stimuli, which is caused by damage to the auditory system in response to excessive levels of noise, ototoxic agents and aging. Neural plasticity, oxidative/nitrosative stress and apoptosis play important roles in the pathogenesis of tinnitus. The expression of neural plasticity related to excessive glutamatergic neurotransmission leads to generation of abnormal sound in one's ears or head. Furthermore, hyperactivation and over-expression of NMDA receptors in response to excessive release of glutamate contribute to the calcium overload in the primary auditory neurons and subsequent cytotox-icity. Reactive oxygen/nitrogen species are endogenously produced by different type of cochlear cells under pathological conditions, which cause direct damage to the intracellular components and apoptotic cell death. Cochlear hair-cell death contributes to the progressive deafferentation of auditory neurons, which consequently leads to the aberrant activity in several parts of the auditory pathway. Therefore, targeting neural plasticity, oxidative/nitrosative stress, apoptosis and autophagy may ameliorate tinnitus. Melatonin is an endogenously produced indoleamine synchronizing circadian and circannual rhythms. Based on laboratory studies indicating the protective effect of melatonin against cochlear damage induced by acoustic trauma and ototoxic agents, and also clinical studies reporting the ability of melatonin to minimize the severity of tinnitus, melatonin is suggested to be a treatment option for the patient with tinnitus. Herein, we describe the ameliorative effect of melatonin on tinnitus, focusing on neural plasticity, oxidative/nitrosative stress, apoptotsis and autophagy.

Original languageEnglish (US)
Pages (from-to)1112-1128
Number of pages17
JournalCurrent drug targets
Issue number11
StatePublished - 2019


  • Apoptosis
  • Autophagy
  • Melatonin
  • Neural plasticity
  • Oxidative stress
  • Tinnitus

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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