Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model
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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2023-09-01
|
Series: | Metabolites |
Subjects: | |
Online Access: | https://www.mdpi.com/2218-1989/13/9/1020 |
_version_ | 1797578905044910080 |
---|---|
author | Liming Gu Wenli Wang Yifeng Gu Jianping Cao Chang Wang |
author_facet | Liming Gu Wenli Wang Yifeng Gu Jianping Cao Chang Wang |
author_sort | Liming Gu |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-10T22:28:19Z |
format | Article |
id | doaj.art-bda1067180ff44ed9ae88ccd567c6fbc |
institution | Directory Open Access Journal |
issn | 2218-1989 |
language | English |
last_indexed | 2024-03-10T22:28:19Z |
publishDate | 2023-09-01 |
publisher | MDPI AG |
record_format | Article |
series | Metabolites |
spelling | doaj.art-bda1067180ff44ed9ae88ccd567c6fbc2023-11-19T11:55:38ZengMDPI AGMetabolites2218-19892023-09-01139102010.3390/metabo13091020Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat ModelLiming Gu0Wenli Wang1Yifeng Gu2Jianping Cao3Chang Wang4State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren’ai Road 199, Suzhou 215123, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren’ai Road 199, Suzhou 215123, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren’ai Road 199, Suzhou 215123, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren’ai Road 199, Suzhou 215123, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren’ai Road 199, Suzhou 215123, ChinaThe 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.https://www.mdpi.com/2218-1989/13/9/1020metabolomicswhole-thorax irradiation (WTI)radiation-induced lung injury (RILI)metabolic markerdynamic |
spellingShingle | Liming Gu Wenli Wang Yifeng Gu Jianping Cao Chang Wang Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model Metabolites metabolomics whole-thorax irradiation (WTI) radiation-induced lung injury (RILI) metabolic marker dynamic |
title | Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model |
title_full | Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model |
title_fullStr | Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model |
title_full_unstemmed | Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model |
title_short | Metabolomic Signatures Associated with Radiation-Induced Lung Injury by Correlating Lung Tissue to Plasma in a Rat Model |
title_sort | metabolomic signatures associated with radiation induced lung injury by correlating lung tissue to plasma in a rat model |
topic | metabolomics whole-thorax irradiation (WTI) radiation-induced lung injury (RILI) metabolic marker dynamic |
url | https://www.mdpi.com/2218-1989/13/9/1020 |
work_keys_str_mv | AT liminggu metabolomicsignaturesassociatedwithradiationinducedlunginjurybycorrelatinglungtissuetoplasmainaratmodel AT wenliwang metabolomicsignaturesassociatedwithradiationinducedlunginjurybycorrelatinglungtissuetoplasmainaratmodel AT yifenggu metabolomicsignaturesassociatedwithradiationinducedlunginjurybycorrelatinglungtissuetoplasmainaratmodel AT jianpingcao metabolomicsignaturesassociatedwithradiationinducedlunginjurybycorrelatinglungtissuetoplasmainaratmodel AT changwang metabolomicsignaturesassociatedwithradiationinducedlunginjurybycorrelatinglungtissuetoplasmainaratmodel |