title: Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study.
abstract: OBJECTIVE
  Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC), a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo.
  
  
  METHODS
  The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed.
  
  
  RESULTS
  EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells.
  
  
  CONCLUSIONS
  This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.forename: Hyang Ae
authors.initials: HA
authors.lastname: Shin
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.forename: Jang Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Young-Taek
authors.initials: YT
authors.lastname: Oh
authors.forename: Keun Hyung
authors.initials: KH
authors.lastname: Park
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002392:Catechin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D011419:Propidium; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013280:Stomatitis / Q000188:drug therapy* / Q000209:etiology*
chemical_list: D017382:Reactive Oxygen Species; D011419:Propidium; D002392:Catechin; D016650:Fluorescein-5-isothiocyanate