title: Glibenclamide, a diabetic drug, prevents acute radiation induced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-κB pathway.
abstract: BACKGROUND
  Acute radiation-induced liver injury is a limitation for hepatoma radiotherapy. Come so far the clinical treatments are insufficient. The effective, specific, low toxicity and novel drugs are in powerful need. Glibenclamide is a common hypoglycemic. Some studies have revealed its relation with intracellular reactive oxygen species, the crucial mediator to radiation injury. This study is aimed to investigate if glibenclamide could act on the acute radiation-induced liver injury.
  
  
  RESULTS
  Glibenclamide mitigated acute radiation-induced liver injury of mice, indicating as regression of hepatocellular edema, reduction of hepatic sinusoid, decline in serum ALP level and reduction of hepatocellular apoptosis. Pretreatment of glibenclamide reduced the radiosensitivity of NCTC-1469 cells. In mechanism, glibenclamide elevated cells membrane potential to up-regulate intracellular reactive oxygen species. The increased reactive oxygen species subsequently activated Akt-NF-κB pathway to promote survival of irradiated cells.
  
  
  METHODS
  BALB/C male mice were intraperitoneal injected with glibenclamide 1 hour before hepatic irradiation. At designed time points the livers were taken to make histological study and bloods were collected to measure serum transaminase. With/without glibenclamide pretreatment the irradiated NCTC-1469 cells were tested apoptosis, viability and proliferation. By western blotting the involved molecules were detected.
  
  
  CONCLUSIONS
  Glibenclamide, prevents acute radiation-induced liver injury of mice via up-regulating intracellular reactive oxygen species and subsequently activating Akt-NF-κB pathway.
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Wang
authors.affiliation: Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China.
authors.forename: Wei You
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Hainan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Bailong
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Cai
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005905:Glyburide / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
chemical_list: D007004:Hypoglycemic Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D005905:Glyburide
keywords: ATP-sensitive potassium channel (KATP); acute radiation-induced liver injury; glibenclamide; membrane potential (MP); reactive oxygen species (ROS)