Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model

Overview

Journal Metabolites

Publisher MDPI

Date 2023 Sep 27

PMID 37755300

Authors

Liming Gu

Wenli Wang

Yifeng Gu

Jianping Cao

Chang Wang

Affiliations

Soon will be listed here.

Abstract

The lung has raised significant concerns because of its radiosensitivity. Radiation-induced lung injury (RILI) has a serious impact on the quality of patients' lives and limits the effect of radiotherapy on chest tumors. In clinical practice, effective drug intervention for RILI remains to be fully elucidated. Therefore, an in-depth understanding of the biological characteristics is essential to reveal the mechanisms underlying the complex biological processes and discover novel therapeutic targets in RILI. In this study, Wistar rats received 0, 10, 20 or 35 Gy whole-thorax irradiation (WTI). Lung and plasma samples were collected within 5 days post-irradiation. Then, these samples were processed using liquid chromatography-mass spectrometry (LC-MS). A panel of potential plasma metabolic markers was selected by correlation analysis between the lung tissue and plasma metabolic features, followed by the evaluation of radiation injury levels within 5 days following whole-thorax irradiation (WTI). In addition, the multiple metabolic dysregulations primarily involved amino acids, bile acids and lipid and fatty acid β-oxidation-related metabolites, implying disturbances in the urea cycle, intestinal flora metabolism and mitochondrial dysfunction. In particular, the accumulation of long-chain acylcarnitines (ACs) was observed as early as 2 d post-WTI by dynamic plasma metabolic data analysis. Our findings indicate that plasma metabolic markers have the potential for RILI assessment. These results reveal metabolic characteristics following WTI and provide new insights into therapeutic interventions for RILI.

Citing Articles

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PMID: 39636341 DOI: 10.1007/s11418-024-01860-9.

References

Trivedi D, Hollywood K, Goodacre R . Metabolomics for the masses: The future of metabolomics in a personalized world. New Horiz Transl Med. 2017; 3(6):294-305. PMC: 5653644. DOI: 10.1016/j.nhtm.2017.06.001. View

Liu H, Lu X, Zhao H, Li S, Gao L, Tian M . Enhancement of Acylcarnitine Levels in Small Intestine of Abdominal Irradiation Rats Might Relate to Fatty Acid β-Oxidation Pathway Disequilibration. Dose Response. 2022; 20(1):15593258221075118. PMC: 8874182. DOI: 10.1177/15593258221075118. View

Wang L, Tang Y, Liu S, Mao S, Ling Y, Liu D . Metabonomic profiling of serum and urine by (1)H NMR-based spectroscopy discriminates patients with chronic obstructive pulmonary disease and healthy individuals. PLoS One. 2013; 8(6):e65675. PMC: 3675021. DOI: 10.1371/journal.pone.0065675. View

Wu J, Chen J, Chen J . Role of Farnesoid X Receptor in the Pathogenesis of Respiratory Diseases. Can Respir J. 2020; 2020:9137251. PMC: 7714608. DOI: 10.1155/2020/9137251. View

Beheshti A, Chakravarty K, Fogle H, Fazelinia H, da Silveira W, Boyko V . Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver. Sci Rep. 2019; 9(1):19195. PMC: 6915713. DOI: 10.1038/s41598-019-55869-2. View

Benderitter M, Vincent-Genod L, Pouget J, Voisin P . The cell membrane as a biosensor of oxidative stress induced by radiation exposure: a multiparameter investigation. Radiat Res. 2003; 159(4):471-83. DOI: 10.1667/0033-7587(2003)159[0471:tcmaab]2.0.co;2. View

Laiakis E, Wang Y, Young E, Harken A, Xu Y, Smilenov L . Metabolic Dysregulation after Neutron Exposures Expected from an Improvised Nuclear Device. Radiat Res. 2017; 188(1):21-34. PMC: 5714588. DOI: 10.1667/RR14656.1. View

Laiakis E, Mak T, Anizan S, Amundson S, Barker C, Wolden S . Development of a metabolomic radiation signature in urine from patients undergoing total body irradiation. Radiat Res. 2014; 181(4):350-61. PMC: 4071158. DOI: 10.1667/RR13567.1. View

Ma X, Zhang Y, Jiang D, Yang Y, Wu G, Wu Z . Protective Effects of Functional Amino Acids on Apoptosis, Inflammatory Response, and Pulmonary Fibrosis in Lipopolysaccharide-Challenged Mice. J Agric Food Chem. 2019; 67(17):4915-4922. DOI: 10.1021/acs.jafc.9b00942. View

10.

Reeds P, Fjeld C, Jahoor F . Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states?. J Nutr. 1994; 124(6):906-10. DOI: 10.1093/jn/124.6.906. View

11.

Inoue A, Kunitoh H, Sekine I, Sumi M, Tokuuye K, Saijo N . Radiation pneumonitis in lung cancer patients: a retrospective study of risk factors and the long-term prognosis. Int J Radiat Oncol Biol Phys. 2001; 49(3):649-55. DOI: 10.1016/s0360-3016(00)00783-5. View

12.

Rogers R, Donahoe M, Costantino J . Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study. Am Rev Respir Dis. 1992; 146(6):1511-7. DOI: 10.1164/ajrccm/146.6.1511. View

13.

Gould R, BELL V, LILLY E . Stimulation of cholesterol biosynthesis from acetate in rat liver and adrenals by whole body x-irradiation. Am J Physiol. 1959; 196(6):1231-7. DOI: 10.1152/ajplegacy.1959.196.6.1231. View

14.

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

15.

Li Y, Li M, Jia W, Ni Y, Chen T . MCEE: a data preprocessing approach for metabolic confounding effect elimination. Anal Bioanal Chem. 2018; 410(11):2689-2699. DOI: 10.1007/s00216-018-0947-4. View

16.

Khan A, Rana P, Devi M, Chaturvedi S, Javed S, Tripathi R . Nuclear magnetic resonance spectroscopy-based metabonomic investigation of biochemical effects in serum of γ-irradiated mice. Int J Radiat Biol. 2010; 87(1):91-7. DOI: 10.3109/09553002.2010.518211. View

17.

Yao X, Xu C, Cao Y, Lin L, Wu H, Wang C . Early metabolic characterization of brain tissues after whole body radiation based on gas chromatography-mass spectrometry in a rat model. Biomed Chromatogr. 2018; 33(3):e4448. DOI: 10.1002/bmc.4448. View

18.

Li Z, Shen Y, Xin J, Xu X, Ding Q, Chen W . Cryptotanshinone alleviates radiation-induced lung fibrosis via modulation of gut microbiota and bile acid metabolism. Phytother Res. 2023; 37(10):4557-4571. DOI: 10.1002/ptr.7926. View

19.

Gao Y, Li X, Gao J, Zhang Z, Feng Y, Nie J . Metabolomic Analysis of Radiation-Induced Lung Injury in Rats: The Potential Radioprotective Role of Taurine. Dose Response. 2019; 17(4):1559325819883479. PMC: 6823985. DOI: 10.1177/1559325819883479. View

20.

Tarasenko T, Cusmano-Ozog K, McGuire P . Tissue acylcarnitine status in a mouse model of mitochondrial β-oxidation deficiency during metabolic decompensation due to influenza virus infection. Mol Genet Metab. 2018; 125(1-2):144-152. PMC: 6626496. DOI: 10.1016/j.ymgme.2018.06.012. View