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    Does melatonin alleviate ototoxic effect caused by administration of cisplatin?
    (2019) Alicura Tokgoz, Sibel; Simsek, Gokce; Vuralkan, Erkan; Caliskan, Murat; Besalti, Omer; Akin, Istemihan
    Aim: In this study, it was aimed to experimentally investigate the protective effects of melatonin in the cisplatin-induced ototoxicity.Material and Methods: Ten Wistar-albino rats were included in the study. Two equal groups were generated randomly as cisplatin and melatonin groups. Rats’ underwent Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) testing before the drug administration and the results were recorded. Both tests were repeated 72 hours after the cisplatin administration in all rats.Results: Significant difference was found between the I-IV interval values before the treatment and after the treatment both in cisplatin and melatonin group. As well as the significant difference in hearing threshold value changes, statistically, significant differences in ABR-I and ABR-IV interval variations were also seen between the cisplatin and melatonin groups. A statistically significant decrease was found between the initial and final control SNR (signal-to-noise ratio) levels within the cisplatin group in the evaluations at 2000Hz, 3000Hz and 4000Hz. Statistically, significant differences were observed between SNR levels when the melatonin group was compared with the cisplatin group. Conclusion: Melatonin appears to reduce cisplatin-induced ototoxicity in rats. Although, the use of supplementary therapies targeting to reduce the toxic effects in clinical studies is still a controversial point.
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    Effects of Topical Phenytoin on Nasal Wound Healing After Mechanical Trauma: An Experimental Study
    (Wiley, 2014) Simsek, Gokce; Ciftci, Osman; Karadag, Nese; Karatas, Erkan; Kizilay, Ahmet
    Objectives/HypothesisImpaired postoperative wound healing is the second most common morbidity after synechia formation in endoscopic sinus surgery. The aim of this experimental study was to investigate the potential effects of topical phenytoin on wound healing after nasal mucosal trauma in rats. Study DesignAn experimental study at the Inonu University Faculty of Medicine. MethodsTwenty-four rats were randomized into three groups: 1) phenytoin group (n=8), 2) control group (n=8), and 3) vehicle group (n=8). After damaging the right nasal cavity, in the phenytoin group, 1% topical phenytoin cream was applied for 7 days. The rats in the control group did not receive any treatment. The vehicle group was treated with daily topical cold cream for 1 week. The rats were sacrificed at the end, and the nasal cavities were excised. Tissue edema and inflammatory cell infiltration were compared among the groups. Additionally, proliferating cell nuclear antigen (PCNA) and cluster of differentiation 31 (CD31) immunoexpression levels were evaluated. Furthermore, in biochemical analysis, the tissue levels of vascular endothelial growth factor and (EGF) of the groups were investigated. ResultsIn the phenytoin group, tissue edema and inflammatory cell infiltration were significantly decreased, and PCNA and CD31 immunoexpression levels were more prominent (P<.001) and the tissue EGF levels were significantly higher (P<.01). ConclusionsTopical phenytoin treatment may alter the nasal wound healing after mechanical trauma. The potential beneficial effects of topical phenytoin on nasal mucosa should be investigated by further experimental and human trials. Level of EvidenceNA Laryngoscope, 124:E449-E454, 2014
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    Melatonin Protects Inner Ear Against Radiation Damage in Rats
    (Wiley, 2015) Karaer, Isil; Simsek, Gokce; Gul, Mehmet; Bahar, Leyla; Gurocak, Simay; Parlakpinar, Hakan; Nuransoy, Ayse
    Objectives/Hypothesis: To examine the effects of N-acetyl-5-methoxytryptamine (melatonin) on radiation-induced inner ear damage. Study Design: An experimental animal model. Methods: Forty rats were randomized into five groups, as follows: 1) melatonin and then radiotherapy group (n = 8), which received intraperitoneal (i.p.) melatonin (5 mg/kg) followed by irradiation 30 minutes later; 2) radiotherapy and then melatonin group (n = 8), which received irradiation with i.p. melatonin (5 mg/kg) 30 minutes later; 3) melatonin group (n = 8), which received i.p. melatonin (5 mg/kg); 4) radiotherapy group (n = 8), which underwent only irradiation; 5) and the control group (n = 8), which received i.p. 0.9% NaCl. The medications and irradiation were administered for 5 days. All rats underwent the distortion product otoacoustic emission (DPOAE) test before and 10 days after the experiment. The middle ears of the rats were excised, and assessment of tissue alterations in the organs of Corti, spiral ganglions, and stria vascularis were compared among the groups. Results: In the radiotherapy group, the DPOAE amplitudes at frequencies of 4000 to 6000 Hz were significantly decreased when compared with the controls. The DPOAE amplitudes both in the melatonin and then radiotherapy group and the radiotherapy and then melatonin group exhibited better values than they did in the radiotherapy group. Histopathological evidence of damage to the organs of Corti, spiral ganglions, and stria vascularis damage was markedly reduced in both these two groups when compared to the radiotherapy group. Conclusion: These results indicate that melatonin may have significant ameliorative effects on cochlear damage secondary to ionizing radiation.
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    Melatonin's protective effect on the salivary gland against ionized radiation damage in rats
    (Wiley, 2016) Karaer, Isil Cakmak; Simsek, Gokce; Yildiz, Azibe; Vardi, Nigar; Polat, Alaadin; Tanbek, Kevser; Gurocak, Simay
    ObjectivesThe aim of this study was to examine the effects of melatonin on ionized radiation-induced salivary gland damage using an experimental model. Materials and MethodsThirty-two rats were randomized into four groups: (i) the control group (C, n = 8) that received intraperitoneal (i.p.) 0.9% NaCl; (ii) the melatonin group (M, n = 8) that received i.p. 5 mg/kg melatonin; (iii) the radiotherapy group (RT, n = 8) that underwent irradiation; (iv) the melatonin plus radiotherapy group (M+RT, n = 8) that received i.p. 5 mg/kg of melatonin, followed by irradiation 30 min later; and (v) the radiotherapy plus melatonin group (RT+M, n = 8) that received irradiation followed by i.p. 5 mg/kg of melatonin 30 min later. The medications and irradiation were administered for 5 days and the salivary glands of the rats were excised 10 days later; the histopathological changes in the salivary glands were assessed and biochemical analyses were conducted (tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI)). ResultsRegardless of whether melatonin was administered before or after radiotherapy, melatonin decreased the radiation-induced parotid and submandibular histological damage. In addition, regardless of whether administration occurred before or after radiotherapy, melatonin decreased oxidative stress markers, such as MDA, TOS, and OSI. On the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin. ConclusionsMelatonin may have a significant protective effect on salivary gland damage secondary to ionizing radiation.
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    Protective effects of resveratrol on salivary gland damage induced by total body irradiation in rats
    (Wiley-Blackwell, 2012) Simsek, Gokce; Gurocak, Simay; Karadag, Nese; Karabulut, Aysun Bay; Demirtas, Erol; Karatas, Erkan; Pepele, Eda
    Objectives/Hypothesis: One of the most common acute side effects of irradiation is xerostomia, which results from damage to the salivary gland cells by direct ionization. Resveratrol is a natural compound with profound anti-inflammatory and antioxidant properties. The purpose of the present study was to investigate the potential protective effects of resveratrol on injury to the salivary glands of rats that were exposed to total body irradiation. Study Design: An experimental study at the Inonu University School of Medicine. Methods: Twenty-nine female rats were randomized into four groups: group 1, high-dose (100 mg/kg) resveratrol group (n = 7); group 2, low-dose (10 mg/kg) resveratrol group (n = 7); group 3, control (vehicle) rats (n = 7); and group 4, sham-irradiation group (n = 8). The medications were administered as single doses, and the rats were exposed to total body irradiation 24 hours after the treatment. The animals were sacrificed the following day, and the parotid and submandibular glands were excised. Salivary gland histology and the tissue levels of glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) were investigated. Results: The rats in group 1 showed significantly decreased acinar loss and less ductal damage and cell necrosis than those of the control group (P < .05). Antioxidant GSH levels were significantly increased by high doses of resveratrol treatment. The tissue activities of MDA in both the parotid and submandibular glands were significantly reduced in group 1. Low-dose resveratrol treatment did not significantly alter the tissue levels of MDA. Conclusions: Resveratrol at relatively high doses can reduce the irradiation-dependent salivary gland damage, suggesting that this natural antioxidant may be effectively used to lessen the side effects related to salivary gland dysfunction that is induced by irradiation. Laryngoscope, 2012