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ABSTRACT: Objectives: Klotho protein is involved in insulin-signalling and ageing. Klotho mutation causes premature ageing and significantly shortens the lifespan. The anti-neoplastic drug cisplatin promotes ototoxicity at higher doses by inducing apoptosis. This study aimed to clarify the effect of klotho expression on cisplatin ototoxicity, using an auditory cell line. Materials and methods: Expressions of klotho messenger RNA and protein were analysed by reverse-transcription polymerase chain reaction and western blotting. Auditory cells (HEI-OC1 line) were pretreated with 2 nM klotho protein for 2 hours; 15 µM cisplatin was then applied. After 48 hours incubation, assessment of cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay), apoptosis (via Hoechst 33258 staining) and reactive oxygen species was performed. Results: Klotho protein expression increased in cisplatin-treated auditory cells. Cells treated with both klotho protein and cisplatin showed a viability of 67.7 per cent, versus 59.4 per cent in cisplatin-treated cells. Klotho significantly attenuated the cisplatin-induced increase in reactive oxygen species, and increased the viability of cells with cisplatin-induced cytotoxicity. Conclusion: Klotho protein is protective against cisplatin-induced auditory cell cytotoxicity; inhibition of reactive oxygen species may be the main mechanism.
The Journal of Laryngology & Otology 08/2012; 126(10):1003-9. · 0.60 Impact Factor
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ABSTRACT: Ras-related C3 botulinum toxin substrate 1 (RAC1) is a 21-kDa signaling G protein that functions as a pleiotropic regulator of many cellular processes including epithelial differentiation. RAC1 activates the nicotinamide adenine dinucleotide phosphate oxidase complex which promotes formation of reactive oxygen species and degradation enzymes. RAC1 has been associated with rapid epithelial differentiation and invasive properties in human cholesteatoma. This study aimed to identify the presence of RAC1 in human cholesteatoma and analyze its functional role as a regulator of proteolysis and overgrowth. Tissue samples from human cholesteatoma and normal postaural skin were obtained from patients during otologic surgery for cholesteatoma. The expression of RAC1 mRNA was quantified by real-time RT-PCR, and localization of RAC1 expression was confirmed using immunohistochemical staining. Expression of RAC1 mRNA in the epithelium of cholesteatoma was significantly elevated 2.94 fold on average, compared with normal control skin. RAC1 expression in the suprabasal and basal layer of cholesteatoma epithelium was stronger than normal control skin. Our results suggest that RAC1 can be associated with rapid epithelial differentiation and invasive properties of human cholesteatoma.
Archives of Oto-Rhino-Laryngology 02/2012; · 1.29 Impact Factor
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ABSTRACT: We report an isolated otosclerosis of the incus that was removed using a transcanal approach and the ossicular chain was reconstructed using a total ossicular replacement prosthesis due to a tilted stapes.
Auris, nasus, larynx 02/2011; 38(5):654-6. · 0.58 Impact Factor
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ABSTRACT: Insulin-like growth factors (IGFs) are known to be neurotrophic factors, and they efficiently signal to cells to grow, differentiate and survive. The purpose of study was to identify the expressions of IGFs in mice with salicylate ototoxicity, which is a typical reversible hearing loss model.
The mice were given intraperitoneal injections of salicylate (400 mg/kg) and about a 30 dB threshold shift was achieved at 3 hours. The expressions of IGF-1 and 2 were confirmed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Localization of IGFs was confirmed using confocal immunofluorescence imaging. For in-vitro study on the HEI-OC1 auditory cells, the cell viability was calculated and the apoptotic features of the nuclei were observed with Hoechst staining.
The expressions of the IGFs mRNA and protein were significantly increased in the salicylate ototoxicity groups compared with that of the normal control group. Salicylate induced apoptosis and decreased viability of the HEI-OC1 auditory cells in a time- and dose-dependent manner. The expressions of IGFs were localized in the stria vascularis, and these IGFs play a protective role in the in-vivo condition of salicylate ototoxicity.
IGFs were highly expressed in the mice with salicylate ototoxicity, and this expression was mainly focused in the stria vascularis in the salicylate intoxicated mice. The systemic action of IGFs, which were expressed in the vascular-rich stria vascularis, can act as a major protective mechanism in a mouse model of salicylate ototoxicity.
Clinical and Experimental Otorhinolaryngology 09/2010; 3(3):115-21. · 0.92 Impact Factor
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ABSTRACT: Ginseng extract is known to have many beneficial effects, including the reversal of pathological and physiological changes induced by ischemia, stress, and aging. Cisplatin, an effective antineoplastic drug, can cause irreversible sensorineural hearing loss and serious tinnitus in humans; thus cisplatin-induced ototoxicity is a useful experimental model for ototoxicity. This study investigated the protective effects of Korean red ginseng extract on cisplatin-induced ototoxicity in auditory cells. Pretreatment with 2.5 mg/mL of ginseng extract prior to application of 20 microM of cisplatin significantly increased cell viability after 48 h of incubation in auditory cells. Pretreatment with ginseng extract significantly attenuated the cisplatin-induced increase in reactive oxygen species (ROS). Ginseng extract also inhibited the expression of caspase-3 and poly-ADP-ribose polymerase related to cisplatin-induced apoptosis because a major mechanism of cisplatin-induced toxicity involves ROS production. Thus, Korean red ginseng extract can play both an anti-apoptotic and anti-oxidative role on cisplatin-induced ototoxicity in an auditory cell line.
Phytotherapy Research 12/2009; 24(4):614-21. · 2.09 Impact Factor
