title: Peanut sprout extract attenuates cisplatin-induced ototoxicity by induction of the Akt/Nrf2-mediated redox pathway.
abstract: OBJECTIVE
  Cisplatin is commonly used to treat solid tumors. However, permanent hearing loss is a major side effect of cisplatin chemotherapy and often results in dose reduction of the cisplatin chemotherapy. Peanut sprouts show cytoprotective properties owing to their antioxidant activities. This study was designed to investigate the effect of peanut sprout extract (PSE) on cisplatin-induced ototoxicity in an auditory cell line, HEI-OC1 cells.
  
  
  METHODS
  Cells were exposed to cisplatin for 24 h, with or without pre-treatment with PSE, cell viability was examined using the MTT assay. Apoptotic cells were identified by double staining with Hoechst 33258 and propidium iodide. Western blot analysis was performed to examine apoptotic proteins including C-PARP and C-caspase, anti-apoptotic protein Bcl-2, and Nrf2 redox system activation. Mitochondrial reactive oxygen species (ROS) were investigated to examine whether PSE could scavenge cisplatin-induced ROS. Real-time PCR analyses were performed to investigate the mRNA levels of antioxidant enzymes including NQO1, HO-1, GPx2, Gclc, and catalase.
  
  
  RESULTS
  The cisplatin-treated group showed reduced cell viability, increased apoptotic properties and markers, and increased ROS levels. PSE pre-treatment before cisplatin exposure significantly increased cell viability and reduced apoptotic properties and ROS production. These effects resulted from the up-regulation of antioxidant genes, including NQO1, HO-1, GPx2, Gclc, and catalase through Akt phosphorylation and Nrf2 activation.
  
  
  CONCLUSIONS
  Our results demonstrate that PSE protects from cisplatin-induced cytotoxicity by activating the antioxidant effects via the Akt/Nrf-2 pathway in this auditory cell line, and indicate that PSE may provide novel treatment to prevent cisplatin-induced ototoxicity.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea; Division of Natural Medical Science, Chosun University School of Medicine, Gwangju, South Korea.
authors.forename: Cha Kyung
authors.initials: CK
authors.lastname: Youn
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea.
authors.forename: Eu-Ri
authors.initials: ER
authors.lastname: Jo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea.
authors.forename: Ju-Hwan
authors.initials: JH
authors.lastname: Sim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea. Electronic address: chosi@chosun.ac.kr.
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Cho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D010367:Arachis; D015153:Blotting, Western; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D005721:Glutamate-Cysteine Ligase / Q000187:drug effects / Q000235:genetics; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000235:genetics; D006198:Hair Cells, Auditory / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D007760:Labyrinth Supporting Cells / Q000187:drug effects*; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D036226:Seedlings; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C052617:Bcl2 protein, mouse; C492172:Gpx2 protein, mouse; D002374:Catalase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D005721:Glutamate-Cysteine Ligase; D002945:Cisplatin
keywords: Apoptosis; Cell death; Cisplatin; Ototoxicity; Peanut sprout