Metformin mitigates gas explosion‑induced blast lung injuries through AMPK‑mediated energy metabolism and NOX2‑related oxidation pathway in rats

Abstract

Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation.

Effects of metformin on acute respiratory distress syndrome in preclinical studies: a systematic review and meta-analysis

“…Effects of metformin on direct ALI were reported in one study ( Zhang M. et al, 2022 ) [SMD = −7.61 (−11.13 to −4.09)]. Indirect ALI was also reduced by metformin [five studies, SMD = 3.72 (−5.07 to −2.37), I 2 = 64.8%].…”

“…Then, we screened, reviewed, and excluded most of these articles as not meeting our criteria stated in the method section. Finally, we included 15 preclinical studies ( Zmijewski et al, 2008 ; Jian et al, 2013 ; Liu et al, 2016 ; Vaez et al, 2016 ; Wang et al, 2016 ; Ghavimi et al, 2018 ; Wu et al, 2018 ; Yu et al, 2018 ; He et al, 2019 ; Wu et al, 2019 ; Xian et al, 2021 ; Zhang Y. et al, 2022 ; Zhang M. et al, 2022 ; Yuan et al, 2022 ; Wan et al, 2023 ) in this meta-analysis. The procedure for study selection is presented in a flow chart in Figure 1 .…”