In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity

[Introduction]: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases. [Aim]: To evaluate the protective...

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Detalles Bibliográficos
Autores: Roldán-Fidalgo, A., Martín-Saldaña, Sergio, Trinidad, A., Olmedilla-Alonso, Begoña, Rodríguez-Valiente, A., García-Berrocal, José Ramón, Ramírez-Camacho, R.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/171567
Acceso en línea:http://hdl.handle.net/10261/171567
Access Level:acceso abierto
Palabra clave:Lutein
Cisplatin
Rat
HEI-OC1
Ototoxicity
Descripción
Sumario:[Introduction]: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases. [Aim]: To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity. [Materials and Methods]: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5–100 μM) and to 25 μM cisplatin for 24 h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n = 8) received intratympanic lutein (0.03 mL) (1 mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n = 8) received also intraperitoneal cisplatin (10 mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n = 12) received intratympanic lutein (0.03 mL) (1 mg/mL) to quantify lutein in cochlear fluids (30 min, 1 h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy. [Results]: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI-OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 μM. In vivo study: Intratympanic lutein (1 mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats. [Conclusions]: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result.