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    Does Calcium Dobesilate Have Therapeutic Effect on Gentamicin-induced Cochlear Nerve Ototoxicity? An Experimental Study
    (Lippincott Williams & Wilkins, 2020) Cinar, Zehra; Edizer, Deniz Tuna; Yigit, Ozgur; Altunay, Zeynep Onerci; Gul, Mehmet; Atas, Ahmet
    Hypothesis: The ototoxic effects of aminoglycosides are well known. Gentamicin carries a substantial risk of hearing loss. Gentamicin is widely used to combat life-threatening infections, despite its ototoxic effects. Calcium dobesilate is a pharmacologically active agent used to treat many disorders due to its vasoprotective and antioxidant effects. We investigated the therapeutic role of calcium dobesilate against gentamicin-induced cochlear nerve ototoxicity in an animal model. Methods: Thirty-two Sprague Dawley rats were divided into four groups: Gentamicin, Gentamicin + Calcium Dobesilate, Calcium Dobesilate, and Control. Preoperative and postoperative hearing thresholds were determined using auditory brainstem response thresholds with click and 16-kHz tone-burst stimuli. Histological analysis of the tympanic bulla specimens was performed under light and transmission electron microscopy. The histological findings were subjected to semiquantitative grading, of which the results were compared between the groups. Results: Gentamicin + Calcium Dobesilate group had, on average, 27 dB better click-evoked hearing than Gentamicin group (p < 0.01), whereas the difference was not significant with 16-kHz tone-burst stimuli (p > 0.01). Histologically examining the Control and Calcium Dobesilate groups revealed normal ultrastructural appearances. The Gentamicin group showed the most severe histological alterations including myelin destruction, total axonal degeneration, and edema. The histological evidence of damage was significantly reduced in the Gentamicin + Calcium Dobesilate group compared with the Gentamicin group. Conclusion: Adding oral calcium dobesilate to systemic gentamicin was demonstrated to exert beneficial effects on click-evoked hearing thresholds, as supported by the histological findings.
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    Effects of Melatonin and Dexamethasone on Facial Nerve Neurorrhaphy
    (Aves, 2019) Edizer, Deniz Tuna; Donmez, Zehra; Gul, Mehmet; Yigit, Ozgur; Yigitcan, Birgul; Adatepe, Turgut; Uzun, Nurten
    OBJECTIVES: To investigate the effects of topical and systemic administrations of melatonin and dexamethasone on facial nerve regeneration. MATERIALS and METHODS: In total, 50 male albino Wistar rats underwent facial nerve axotomy and neurorrhaphy. The animals were divided into 5 groups: control, topical melatonin, systemic melatonin, topical dexamethasone, and systemic dexamethasone. Nerve conduction studies were performed preoperatively and at 3, 6, 9, and 12 weeks after drug administrations. Amplitude and latency of the compound muscle action potentials were recorded. Coapted facial nerves were investigated under light and electron microscopy. Nerve diameter, axon diameter, and myelin thickness were recorded quantitatively. RESULTS: Amplitudes decreased and latencies increased in both the melatonin and dexamethasone groups. At the final examination, the electrophysiological evidence of facial nerve degeneration was not significantly different between the groups. Histopathological examinations revealed the largest nerve diameter in the melatonin groups, followed by the dexamethasone and control groups (p<0.05). Axon diameter of the control group was smaller than those of the melatonin (topical and systemic) and topical dexamethasone groups (p<0.05). The melatonin groups had almost normal myelin ultrastructure. CONCLUSION: Electrophysiological evaluation did not reveal any potential benefit of dexamethasone and melatonin in contrast to histopathological examination, which revealed beneficial effects of melatonin in particular. These agents may increase the regeneration of facial nerves, but electrophysiological evidence of regeneration may appear later.
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    Protective role of intratympanic nigella sativa oil against gentamicin induced hearing loss
    (Elsevier Ireland Ltd, 2017) Edizer, Deniz Tuna; Yigit, Ozgur; Cinar, Zehra; Gul, Mehmet; Kara, Eyyup; Yigitcan, Birgul; Hayir, Duygu
    Objective: Aminoglycosides, used to combat with life-threatening infections, have a substantial risk of hearing loss. Nigella sativa is an annual herbaceous plant and used for treatment of many diseases for ages. We aimed to investigate the protective role of intratympanic nigella sativa oil against gentamicin induced hearing loss in an animal model. Methods and materials: Twenty eight guinea pigs were randomly divided into four groups: i-control, ii-Intratympanic nigella sativa oil (IT-NSO), Intraperitoneal gentamicin (IP-G) and iv- Intraperitoneal gentamicin and intratympanic nigella sativa oil (IP-G + IT-NSO). Preoperative and postoperative hearing thresholds were determined with auditory brainstem response with click and 8 kHz tone-burst stimuli. Histological analysis of the cochlea specimens were performed under light microscope. Semiquantitative grading of the histological findings was carried out and compared between the groups. Results: Highest posttreatment hearing thresholds were detected in IP-G group. Posttreatment mean hearing threshold of the IP-G group with click stimulus was significantly higher than the IP-G + IT-NSO group (p = 0.004). whereas the difference was not significant with 8 kHz tone-burst stimulus (p = 0.137). Both IP-G and IP-G + IT-NSO groups had significantly higher hearing thresholds compared to control and IT-NSO groups (p > 0.05). Histological examination of the control and IT-NSO groups demonstrated normal appearance of cochlear nerve, stria vascularis and organ of Corti. IP-G group showed the most severe histological alterations including hydropic and vacuolar degenerations, hair cell damage and deformation of the basilar mambrane. Histological evidence of damage was significantly reduced in IP- G + IT-NSO group compared to IP-G group. Conclusion: Addition of intratympanic NSO to systemic gentamicin was demonstrated to have beneficial effects in hearing thresholds which was supported by histological findings. (C) 2017 Elsevier B.V. All rights reserved.