Glibenclamide, a diabetic drug, prevents acute radiationinduced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-κB pathway.

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Glibenclamide, a diabetic drug, prevents acute radiationinduced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-κB pathway.

Oncotarget. 2017 Mar 23;:

Authors: Liu H, Wang S, Wu Z, Huang Z, You Chen W, Yang Y, Cui J, Liu C, Zhao H, Guo J, Zhang P, Gao F, Li B, Cai J

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.

PMID: 28380448 [PubMed - as supplied by publisher]

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