Yining Zhang, Tao Yan, Wei Mo, Bin Song, Yuehua Zhang, Fenghao Geng, Zhimin Hu, Daojiang Yu, Shuyu Zhang
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The <i>in vivo</i> radioprotective effect of deoxycholic acid (DCA) was detected in irradiated SD rats.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Ionizing radiation modulates the metabolism of BAs. DCA is a prospective therapeutic agent for the treatment of RSI.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Altered bile acid metabolism in skin tissues in response to ionizing radiation: deoxycholic acid (DCA) as a novel treatment for radiogenic skin injury.\",\"authors\":\"Yining Zhang, Tao Yan, Wei Mo, Bin Song, Yuehua Zhang, Fenghao Geng, Zhimin Hu, Daojiang Yu, Shuyu Zhang\",\"doi\":\"10.1080/09553002.2023.2245461\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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 <i>in vivo</i> radioprotective effect of deoxycholic acid (DCA) was detected in irradiated SD rats.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Ionizing radiation modulates the metabolism of BAs. 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引用次数: 1
摘要
目的：放射性皮肤损伤（RSI）是癌症放疗或意外暴露于辐射时常见的并发症。本研究旨在调查 RSI 期间胆汁酸（BA）及其衍生物的代谢情况：方法：用 X 射线直线加速器照射大鼠皮肤组织。方法：用 X 射线加速器照射大鼠皮肤组织，采用液相色谱-质谱法（LC-MS）定量分析胆汁酸及其衍生物。通过单细胞RNA测序（scRNA-Seq）数据分析了人类患者和动物模型RSI中BA生物合成的关键酶。检测了脱氧胆酸（DCA）在辐照 SD 大鼠体内的放射保护作用：结果：12 种 BA 代谢物在 RSI 进展过程中表现出显著差异。12-ketolithocholic acid (12-ketoLCA) 和熊去氧胆酸 (UDCA)在辐照皮肤中明显升高，而石胆酸 (LCA)、牛磺酸-β-甲基胆酸 (Tβ-MCA) 和牛磺酸 (TCA) 则明显降低。此外，scRNA-Seq 的结果表明，在皮肤成纤维细胞或角质细胞中，参与 BA 合成第一步 7a-hydroxylation 过程的基因发生了明显的变化。电离辐射后，BA 合成的替代途径比经典途径的改变更为活跃。在大鼠放射性皮肤损伤模型中，DCA 可促进伤口愈合并减轻表皮增生：结论：电离辐射可调节生物碱的代谢。结论：电离辐射可调节 BAs 的代谢，DCA 是一种治疗 RSI 的前瞻性药物。
Altered bile acid metabolism in skin tissues in response to ionizing radiation: deoxycholic acid (DCA) as a novel treatment for radiogenic skin injury.
Objective: 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.
Methods: 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.
Results: 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.
Conclusions: Ionizing radiation modulates the metabolism of BAs. DCA is a prospective therapeutic agent for the treatment of RSI.
期刊介绍：
The International Journal of Radiation Biology publishes original papers, reviews, current topic articles, technical notes/reports, and meeting reports on the effects of ionizing, UV and visible radiation, accelerated particles, electromagnetic fields, ultrasound, heat and related modalities. The focus is on the biological effects of such radiations: from radiation chemistry to the spectrum of responses of living organisms and underlying mechanisms, including genetic abnormalities, repair phenomena, cell death, dose modifying agents and tissue responses. Application of basic studies to medical uses of radiation extends the coverage to practical problems such as physical and chemical adjuvants which improve the effectiveness of radiation in cancer therapy. Assessment of the hazards of low doses of radiation is also considered.
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