Acetyl-L-Carnitine protects HEI-OC1 auditory cells from radiation and cisplatin induced toxicity

ALTUN Z. S., Pamukoglu A., OLGUN Y., AKTAŞ S., ÇETİNAYAK H. O., KIRKIM G., ...Daha Fazla

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, cilt.9, sa.7, ss.13605-13614, 2016 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 9 Sayı: 7
  • Basım Tarihi: 2016
  • Dergi Adı: INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.13605-13614
  • Anahtar Kelimeler: HEI-OC1, ototoxicity, radiotherapy, cisplatin, Nrf2, Aceytl-L-Carnitine, INFLAMMATORY CYTOKINES, GAMMA-IRRADIATION, OXIDATIVE STRESS, OTOTOXICITY, APOPTOSIS, DAMAGE
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Concomitant applications of CDDP and RT have synergistic effects in oncology. CDDP and RT can cause ototoxicity through oxidative stress. Nrf2 is a transcription factor that has antioxidant properties. The aim of this study is to evaluate the protective effect of ALC via Nrf2 and target genes against CDDP and RT induced ototoxicity in The House Ear Research Institute-Organ of Corti I cells (HEI-OC1). HEI-OC1 cells were exposed to a single dose of 5 Gray RT. After incubation for 72 h with or without ALC, CDDP, and their combinations, ototoxicity of HEI-OC1 cells were examined through analyzing apoptosis, oxidative stress and Nrf2 and related gene expressions by TUNEL, flow cytometry, HPLC and quantitative real-time PCR. ALC protected from RT, CDDP and CDDP-RT induced cell death by inhibiting apoptosis and oxidative stress. ALC-CDDP-RT treatment increased the expressions of Quinone oxidoreductase1 (NQO1), SODIII, Heme Oxygenase (HO-1) and Glutathione-S Transferase (GST). In conclusion, Nuclear factor erythroid 2-related factor 2 (Nrf2) and oxidative stress might play important roles in cisplatin (CDDP), radiotherapy (RT) and CDDP-RT induced ototoxicity. Therefore, targeting Nrf2 by Aceytl-L-Carnitine (ALC) might be potential therapeutic strategies.