title: In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity.
  
  
  METHODS
  In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 μM) and to 25 μM cisplatin for 24h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n=8) received intratympanic lutein (0.03 mL) (1mg/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 (10mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n=12) received intratympanic lutein (0.03 mL) (1mg/mL) to quantify lutein in cochlear fluids (30 min, 1h 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 (1mg/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.
authors: Department of Otorhinolaryngology, Hospital Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: amayarf@gmail.com.
authors: A
authors: A
authors: Roldán-Fidalgo
authors: Foundation for Biomedical Research, Puerta de Hierro Hospital, Madrid, Spain.
authors: S
authors: S
authors: Martín Saldaña
authors: Department of Otorhinolaryngology, Hospital Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Madrid, Spain.
authors: A
authors: A
authors: Trinidad
authors: Institute of Food Science, Technology and Nutrition, CSIC, Madrid, Spain.
authors: B
authors: B
authors: Olmedilla-Alonso
authors: Department of Otorhinolaryngology, Hospital Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Madrid, Spain.
authors: A
authors: A
authors: Rodríguez-Valiente
authors: Department of Otorhinolaryngology, Hospital Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Madrid, Spain.
authors: J R
authors: JR
authors: García-Berrocal
authors: Department of Otorhinolaryngology, Hospital Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Madrid, Spain.
authors: R
authors: R
authors: Ramírez-Camacho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001309:Auditory Threshold / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D014975:Lutein / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology* / Q000633:toxicity; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D020011:Protective Agents; D002945:Cisplatin; D014975:Lutein
keywords: Cisplatin; HEI-OC1; Lutein; Ototoxicity; Rat