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Molecular Aspects of Melatonin Treatment in Tinnitus: A Review

[ Vol. 20 , Issue. 11 ]


Azam Hosseinzadeh, Seyed Kamran Kamrava, Brian C.J. Moore, Russel J. Reiter, Habib Ghaznavi, Mahboobeh Kamali and Saeed Mehrzadi*   Pages 1112 - 1128 ( 17 )


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 cytotoxicity. 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.


Tinnitus, melatonin, neural plasticity, oxidative stress, autophagy, apoptosis.


Razi Drug Research Center, Iran University of Medical Sciences, Tehran, ENT and Head & Neck Research Center, Hazrate Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Department of Psychology, University of Cambridge, Cambridge, Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX, Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Health Promotion Research Center, Iran University of Medical Sciences, Tehran, Razi Drug Research Center, Iran University of Medical Sciences, Tehran

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