Glibenclamide, a diabetic drug, prevents acute radiation-induced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt–NF-κB pathway
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Hu Liu1,*, Shichao Wang2,*, Zhao Wu2,*, Ziyun Huang2, Wei you Chen2, Yanyong Yang1, Jianguo Cui1, Cong Liu1, Hainan Zhao1, Jiaming Guo1, Pei Zhang1, Fu Gao1, Bailong Li1 and Jianming Cai1
1Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
2Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China
*These authors have contributed equally to this work
Fu Gao, email: firstname.lastname@example.org
Bailong Li, email: email@example.com
Jianming Cai, email: firstname.lastname@example.org
Keywords: acute radiation-induced liver injury, reactive oxygen species (ROS), ATP-sensitive potassium channel (KATP), membrane potential (MP), glibenclamide
Received: August 05, 2016 Accepted: February 15, 2017 Published: March 23, 2017
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.
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