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: Hu Liu, Shichao Wang, Zhao Wu, Ziyun Huang, Wei You Chen, Yanyong Yang, Jianguo Cui, Cong Liu, Hainan Zhao, Jiaming Guo, Pei Zhang, Fu Gao, Bailong Li, Jianming Cai
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 25 Pg. 40568-40582 (Jun 20 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28380448 (Publication Type: Journal Article)

Chemical References

• Hypoglycemic Agents
• NF-kappa B
• Reactive Oxygen Species
• Proto-Oncogene Proteins c-akt
• Glyburide

Topics

• Acute Disease
• Animals
• Apoptosis (drug effects, radiation effects)
• Cell Line
• Cell Survival (drug effects, radiation effects)
• Glyburide (pharmacology)
• Hep G2 Cells
• Humans
• Hypoglycemic Agents (pharmacology)
• Liver (drug effects, metabolism, radiation effects)
• Male
• Mice, Inbred BALB C
• NF-kappa B (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Radiation Injuries, Experimental (metabolism, pathology, prevention & control)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects, radiation effects)
• Up-Regulation (drug effects, radiation effects)