Integrative Metabolic Signatures for Hepatic Radiation Injury.
Integrative Metabolic Signatures for Hepatic Radiation Injury.
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DOI：
10.1371/journal.pone.0124795
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Guha C
中科院分区：
文献类型：
--
作者：
Kurland IJ;Broin PÓ;Golden A;Su G;Meng F;Liu L;Mohney R;Kulkarni S;Guha C
放射诱发的肝病 (RILD) 是肝癌放射治疗 (RT) 的剂量限制因素，因此早期检测放射相关的肝损伤对于医疗干预至关重要。代谢组学方法被用来确定代谢特征，这些特征可以作为早期检测小鼠 RILD 的生物标志物。麻醉的 C57BL/6 小鼠接受 0、10 或 50 Gy 全身肝脏照射 (WLI)，并与接受 10 Gy 全身照射 (WBI) 的小鼠形成对比。照射后24小时收集肝脏和血浆样本。使用气相色谱/质谱和液相色谱/质谱对样品进行处理。 WLI 后 24 小时，肝脏样本中检测到 407 种代谢物，血浆中检测到 347 种代谢物。与 50 Gy WLI 相关的血浆代谢物包括多种氨基酸、嘌呤和嘧啶代谢物、微生物代谢物，最显着的是缓激肽和 3-吲哚基硫酸盐。与 50 Gy WLI 相关的肝脏代谢物包括肝脏中的磷酸戊糖、嘌呤和嘧啶代谢物。 WLI 和 WBI 之间共同的血浆生物标志物富含微生物代谢物，如 3-吲哚硫酸盐、吲哚-3-乳酸、苯乳酸、哌啶酸、马尿酸，以及 DNA 损伤标志物，如 2-脱氧尿苷。与色氨酸和吲哚相关的代谢物可能反映辐射引起的肠道微生物组的影响。 WBI 和 WLI 之间共同的主要肝脏生物标志物是氨基酸、糖、TCA 代谢物（富马酸盐）、脂肪酸（亚麻酸、正十六烷酸）和 DNA 损伤标志物（尿苷）。我们鉴定了一组代谢组标记物，这些标记物可能被证明可用作 RILD 和 WBI 的血浆生物标记物。通路分析还表明，肝脏照射后观察到的独特代谢变化是肠、肝和肾的综合反应。
Radiation-induced liver disease (RILD) is a dose-limiting factor in curative radiation therapy (RT) for liver cancers, making early detection of radiation-associated liver injury absolutely essential for medical intervention. A metabolomic approach was used to determine metabolic signatures that could serve as biomarkers for early detection of RILD in mice. Anesthetized C57BL/6 mice received 0, 10 or 50 Gy Whole Liver Irradiation (WLI) and were contrasted to mice, which received 10 Gy whole body irradiation (WBI). Liver and plasma samples were collected at 24 hours after irradiation. The samples were processed using Gas Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry. Twenty four hours after WLI, 407 metabolites were detected in liver samples while 347 metabolites were detected in plasma. Plasma metabolites associated with 50 Gy WLI included several amino acids, purine and pyrimidine metabolites, microbial metabolites, and most prominently bradykinin and 3-indoxyl-sulfate. Liver metabolites associated with 50 Gy WLI included pentose phosphate, purine, and pyrimidine metabolites in liver. Plasma biomarkers in common between WLI and WBI were enriched in microbial metabolites such as 3 indoxyl sulfate, indole-3-lactic acid, phenyllactic acid, pipecolic acid, hippuric acid, and markers of DNA damage such as 2-deoxyuridine. Metabolites associated with tryptophan and indoles may reflect radiation-induced gut microbiome effects. Predominant liver biomarkers in common between WBI and WLI were amino acids, sugars, TCA metabolites (fumarate), fatty acids (lineolate, n-hexadecanoic acid) and DNA damage markers (uridine). We identified a set of metabolomic markers that may prove useful as plasma biomarkers of RILD and WBI. Pathway analysis also suggested that the unique metabolic changes observed after liver irradiation was an integrative response of the intestine, liver and kidney.
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影响因子：
2.6
作者：
Coy SL;Cheema AK;Tyburski JB;Laiakis EC;Collins SP;Fornace A Jr
通讯作者：
Fornace A Jr
影响因子：
3.4
作者：
Johnson CH;Patterson AD;Krausz KW;Lanz C;Kang DW;Luecke H;Gonzalez FJ;Idle JR
通讯作者：
Idle JR
DOI：
10.1016/0360-3016(92)90651-w
发表时间：
1992-01-01
影响因子：
7
作者：
LAWRENCE, TS;TENHAKEN, RK;LICHTER, AS
通讯作者：
LICHTER, AS
影响因子：
19.6
作者：
Huang, KC;Yang, CC;Chien, CT
通讯作者：
Chien, CT
DOI：
10.1111/nyas.12116
发表时间：
2013-01-01
期刊：
ANNALS MEETING REPORTS
影响因子：
--
作者：
Kurland, Irwin J.;Accili, Domenico;Gross, Steven S.
通讯作者：
Gross, Steven S.