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Altered bile acid metabolism in skin tissues in response to ionizing radiation: deoxycholic acid (DCA) as a novel treatment for radiogenic skin injury.

Authors :
Zhang, Yining
Yan, Tao
Mo, Wei
Song, Bin
Zhang, Yuehua
Geng, Fenghao
Hu, Zhimin
Yu, Daojiang
Zhang, Shuyu
Source :
International Journal of Radiation Biology; 2024, Vol. 100 Issue 1, p87-98, 12p
Publication Year :
2024

Abstract

Radiogenic skin injury (RSI) is a common complication during cancer radiotherapy or accidental exposure to radiation. The aim of this study is to investigate the metabolism of bile acids (BAs) and their derivatives during RSI. Rat skin tissues were irradiated by an X-ray linear accelerator. The quantification of BAs and their derivatives were performed by liquid chromatography–mass spectrometry (LC–MS)-based quantitative analysis. Key enzymes in BA biosynthesis were analyzed from single-cell RNA sequencing (scRNA-Seq) data of RSI in the human patient and animal models. The in vivo radioprotective effect of deoxycholic acid (DCA) was detected in irradiated SD rats. Twelve BA metabolites showed significant differences during the progression of RSI. Among them, the levels of cholic acid (CA), DCA, muricholic acid (MCA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), glycohyodeoxycholic acid (GHCA), 12-ketolithocholic acid (12-ketoLCA) and ursodeoxycholic acid (UDCA) were significantly elevated in irradiated skin, whereas lithocholic acid (LCA), tauro-β-muricholic acid (Tβ-MCA) and taurocholic acid (TCA) were significantly decreased. Additionally, the results of scRNA-Seq indicated that genes involved in 7a-hydroxylation process, the first step in BA synthesis, showed pronounced alterations in skin fibroblasts or keratinocytes. The alternative pathway of BA synthesis is more actively altered than the classical pathway after ionizing radiation. In the model of rat radiogenic skin damage, DCA promoted wound healing and attenuated epidermal hyperplasia. Ionizing radiation modulates the metabolism of BAs. DCA is a prospective therapeutic agent for the treatment of RSI. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09553002
Volume :
100
Issue :
1
Database :
Complementary Index
Journal :
International Journal of Radiation Biology
Publication Type :
Academic Journal
Accession number :
174684752
Full Text :
https://doi.org/10.1080/09553002.2023.2245461