Dynamic Metabolic Characterization of Lung Tissues in Rats Exposed to Whole‐Thorax Irradiation Based on GC‐MS

ABSTRACT An animal model of radiation‐induced lung injury (RILI) was established using female rats given sublethal whole‐thorax X‐ray irradiation (15 Gy) at a dose rate of 2.7 Gy/min. The rats were studied for up to day 45 and compared with sham‐irradiated controls. Time‐series lung tissue samples during the progression of RILI were collected for dynamic metabolomics studies based on gas chromatography–mass spectrometry (GC‐MS). Differential metabolites associated with radiation‐induced lung injury were identified, followed by metabolite set enrichment analysis to uncover pathway changes in RILI. The results revealed dynamic metabolic alterations in the progression of RILI, primarily involving in glycine and serine metabolism, the urea cycle, the Warburg effect, glutamate metabolism, arginine and proline metabolism, glucose‐alanine cycle, and ammonia recycling. In addition, the potential panel of biomarkers including taurine, lysine, and tyrosine of RILI was selected and then applied to evaluate the diagnostic potential for RILI based on the receiving operator characteristic curve (ROC) at the early‐stage of RILI. The better sensitivity, specificity, and accuracy indicate the potential of early diagnosis for RILI. These findings suggest that dynamic metabolomics data could provide new insights into understanding the complex metabolic dysregulation underlying RILI, facilitating the selection of biomarkers for early diagnosis.