Evaluation of Gas Explosion Injury Based on Analysis of Rat Serum Profile by Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabonomics Techniques

Abstract

Gas explosion can lead to serious global public health issues. Early period gas explosion injury (GEI) can induce a series of histopathologic and specific metabolic changes. Unfortunately, it is difficult to treat GEI thoroughly. To date, the specific molecular mechanism of GEI is still unclear. To accurately diagnose and provide comprehensive clinical intervention, we performed a global analysis of metabolic alterations involved in GEI. The physiological and behavioral indicators’ changes of rats after gas explosion were observed. These metabolic alterations were first investigated in a rat model using serum metabonomics techniques and multivariate statistical analysis. Significant heart rate (HR), mean blood pressure (mBP), and neurobehavioral index changes were observed in the GEI group after gas explosion. UPLC-MS revealed evident separated clustering between the control and GEI groups using supervised partial least squares discriminant analysis (PLS-DA). We designed an integrated metabonomics study for identifying reliable biomarkers of GEI using a time-course analysis of discriminating metabolites in this experiment. The metabonomics analysis showed alterations in a number of biomarkers (21 from serum). The meaningful biomarkers of GEI provide new insights into the pathophysiological changes and molecular mechanisms of GEI, including the disturbances in oxidative stress and neuroinflammatory reaction, as well as in metabolism of lipids, glucose, and amino acids in rats, suggesting that the process of GEI in humans is likely to be comprehensive and dynamic. Correlations between the GEI group and the biomarkers identified from the rat model will be further explored to elucidate the metabolic pathways responsible for GEI in the human body.

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

“…By investigating the activities of the rate-limiting enzymes in the TCA cycle, specifically α-KGDH and ICDHm, the present study revealed that ATP content was decreased, and the TCA cycle was inhibited after the gas explosion. Similarly, a previous study demonstrated that the rapid consumption of energy by rats with gas explosion-induced injury downregulates galactose metabolism and the TCA cycle, both of which are consistent with the Warburg effect (6). In addition, the present study revealed that gas explosions not only inhibited oxidative phosphorylation but also affected glycolysis.…”

“…Previous studies have indicated that shock waves from a gas explosion contribute damage to the cavity viscera, such as the lungs and brain ( 27 , 28 ). The mechanism of gas explosion-induced lung injury is unclear, and our previous metabolomic study identified nine different metabolites that differ significantly between the control rats and explosion-induced acute lung injury rats ( 6 ). The identified biomarkers reflect well-known adverse health effects of a gas explosion, such as inflammation and impairment of glucose homeostasis ( 29 ).…”

“…rats exposed to gas explosion (6). This abnormality in energy metabolism is probably closely associated with mitochondrial function.…”

“…Mitochondria are important organelles involved in adenosine triphosphate (ATP) synthesis that produce ATP and numerous other biosynthetic intermediates. Our previous study revealed that energy is consumed rapidly and that galactose metabolism and the tricarboxylic acid (TCA) cycle are downregulated in rats exposed to gas explosion ( 6 ). This abnormality in energy metabolism is probably closely associated with mitochondrial function.…”

Establishment and evaluation of an in vitro blast lung injury model using alveolar epithelial cells

“…Mechanistically, damage in alveolar epithelial cells is the main cause of oxidative stress and inflammatory response, it plays an important role in blast wave-induced lung injury (15). Therefore, a lung injury model based on alveolar epithelial cell is particularly useful for mechanistic studies, especially considering the high cost and difficulties in energy control in establishing animal blast lung injury models (16). Herein, to establish a stable, reliable and flexible in vitro model, we exposed the alveolar epithelial cells with specified energies of blast wave and examined the appearance of blast injury.…”