Therapeutic and protective effects of autologous serum in amikacin-induced ototoxicity I B ARSLAN 1 , G G ASLAN 1 , G C MERCAN 1 , S VATANSEVER 2 , I CUKUROVA 1 , S GOKALP 2 , A ASLAN 3 1 ENT Clinic, Tepecik Research and Training Hospital, Izmir, and Departments of 2 Histology, and 3 ORL, Celal Bayar University School of Medicine, Manisa, Turkey Abstract Objective: Possible therapeutic and protective benefits of intratympanic autologous serum application in amikacin- induced ototoxicity were investigated. Methods: Twenty-four guinea pigs were separated equally into two groups: therapeutic (group A) and protective (group B). Transient evoked otoacoustic emissions were recorded before and after autologous serum application. Apoptotic cells were identified in the organ of Corti, spiral limbus and spiral ganglion by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (‘TUNEL’) method. Results: Transient evoked otoacoustic emission responses at 1, 1.4 and 2.8 kHz improved without significance after autologous serum application in group A ( p > 0.05). A significantly protective effect of autologous serum was determined at 4 kHz in group B ( p < 0.05). There were significantly fewer apoptotic cells at the spiral limbus in the therapeutic and protective groups compared to the control group ( p < 0.05). Conclusion: Autologous serum may offer protection against ototoxicity-induced hearing loss, but it cannot restore hearing. Immunohistochemically, autologous serum significantly decreases activation of the intrinsic pathway of pro-apoptotic signalling in mesenchymal cells compared to neurons and neurosensory cells. Key words: Autologous Serum; Ototoxicity; Apoptosis; Organ Of Corti; Spiral Limbus; Ganglion Cell Introduction Ototoxicity is a severe side effect of aminoglycoside antibiotics and may result in sensorineural hearing loss. This hearing loss may be permanent and bilateral, and there is no specific therapy for it. 1,2 Histological studies have revealed that aminoglycoside-induced oto- toxicity begins in the outer hair cells at the basal portion of the cochlea and subsequently affects the inner hair cells. The degeneration of nerve fibres, spiral ganglion neurons and supporting cells is second- ary to hair cell damage. 3,4 Many reports have discussed possible prevention methods for ototoxicity, such as anti-inflammatory drugs, antioxidants, apoptosis inhi- bitors, neuroprotective compounds, neurotrophic factors and gene therapeutic approaches. 2,5,6 In recent decades, stem cells have also been used to replace defi- cient cell types in order to restore hearing. 7 Serum is a complex mixture of factors and molecules involved in cell growth. Growth factors are biologically active polypeptides produced by the body that can stimulate cell division, growth and differentiation. 8 In addition, healing factors such as nerve growth factor, epidermal growth factor, transforming growth factor β, platelet-derived growth factors and insulin-like growth factor-1 are present in both diluted and undiluted serum. 9 Nerve growth factor is the best- known neurotrophic factor; it is responsible for the growth and survival of developing neurons, and the maintenance of mature neurons. 10,11 Recent studies have indicated the efficacy of autologous serum in the treatment of neurotrophic keratopathy, osteoarth- ritis, chronic graft-versus-host disease and tympanic membrane perforations. 11 – 13 In addition to treatment, autologous serum should be able to prevent or at least decrease cell damage via its anti-apoptotic factors. 14 It is these potentially beneficial substances that may provide medical benefits to diseased or damaged inner-ear cells and nerves, in a therapeutic and protect- ive manner. 11,15 Apoptosis can be induced in cells by application of aminoglycosides. The terminal deoxynucleotidyl trans- ferase-mediated dUTP (2 ´ -deoxyuridine, 5 ´ -triphosphate) nick-end labelling (‘TUNEL’) technique has been extensively used in the detection and quantification of Presented at the 30th Politzer Society Meeting, 30 June – 4 July 2015, Niigata, Japan. Accepted for publication 4 August 2017 First published online 20 November 2017 The Journal of Laryngology & Otology (2018), 132, 33–40. MAIN ARTICLE © JLO (1984) Limited, 2017 doi:10.1017/S0022215117002304 https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022215117002304 Downloaded from https://www.cambridge.org/core. IP address: 181.214.134.40, on 16 Apr 2019 at 16:58:26, subject to the Cambridge Core terms of use, available at