Liraglutide Ameliorates Gamma Radiation-Induced Hepatic Damage in Rats: The Role of an Autophagy Flux Activation via LKB1/AMPK/mTOR Axis.

AIM: Radiation-induced hepatotoxicity is a major challenge during radiotherapy. This study aims to evaluate the potential ameliorative outcome and underlying mechanisms of liraglutide (LIRA) in mitigating acute liver injury caused by radiation exposure in vivo. METHODS: Animals were administered LIRA subcutaneously (50 µg/kg/twice daily) for two weeks, and then exposed to whole body γ-radiation (6 Gy) 1 h after the last LIRA dose. RESULTS: The results revealed that LIRA efficiently ceased radiation-induced hepatotoxicity. Autophagy is a vital process for maintaining cellular balance and LIRA boosted it by upregulating the expression of the autophagy markers AMPK (adenosine monophosphate-activated protein kinase) and LKB1 (liver kinase B1), and downregulating mTOR (mammalian target of rapamycin). Furthermore, LIRA maintained liver enzyme levels close to baseline, and inhibited oxidative stress by decreasing lipid peroxidation and stimulating the production of antioxidant enzymes and reduced glutathione (GSH). Moreover, Western blotting confirmed that LIRA blocked the inflammatory response in liver tissues by decreasing the expression of nuclear factor kappa B (NF-κB) and interleukin-1 beta (IL-1β), and increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf) relative proteins. Histological analysis using hematoxylin and eosin (H&E) staining proved that LIRA effectively restored liver tissue architecture. CONCLUSION: Collectively, LIRA attenuated radiation-induced hepatotoxicity by modulating the LKB1/AMPK/mTOR pathway, and could be a promising radioprotector during radiotherapy.