Yang Pengfei, Deng Fenfen, Yuan Mengdi, Chen Meng, Zeng Li, Ouyang Yanan, Chen Xiangbo, Zhao Bin, Yang Zhe, Tian Zhongmin
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Life Sci. 2023 Feb 1;314:121355. doi: 10.1016/j.lfs.2022.121355. Epub 2022 Dec 31.
This study mainly evaluated the protective mechanism of histidine against the hepatic oxidative stress after high-salt exposure (HSE) through combined analysis of non-targeted metabolomics and biological metabolic networks.
Dahl salt-sensitive (SS) rats were fed with normal-salt diet or HSE ± histidine in addition to drinking water for 14 days. Gas chromatography-mass spectrometry was used to analyze the hepatic metabolites. The metabolic profile was analyzed by SIMCA-14.1, the metabolic correlation network was performed using Gephi-0.9.2, and pathway enrichment was analyzed using MetaboAnalyst 5.0 online website.
Results indicated that HSE disturbed the hepatic metabolic profile, generated abnormal liver metabolism and exacerbated oxidative stress. Histidine supplementation significantly reversed the hepatic metabolic profile. Of note, 14 differential metabolic pathways were enriched after histidine supplementation, most of which played an important role in ameliorating redox and nitric oxide (NO) metabolism. Histidine administration decreased the levels of hydroperoxide and malondialdehyde, and increased the activities of antioxidant enzymes (Catalase, Superoxide Dismutase, Glutathione S-transferase and Glutathione reductases). Histidine effectively enhanced the endogenous synthesis of glutathione by increasing the levels of glutamate and cysteine, thereby enhancing the antioxidant capacity of the glutathione system. After histidine administration, lysine, glutamate, and hypotaurine owned a higher metabolic centrality in the correlation network. In addition, histidine could also effectively increase the endogenous synthesis of NO by enhancing the -arginine/NO pathway.
This study offers new insights into the metabolic mechanisms underlying the antioxidant protective effect of histidine on the liver.
本研究主要通过非靶向代谢组学和生物代谢网络的联合分析，评估组氨酸对高盐暴露（HSE）后肝脏氧化应激的保护机制。
除饮用水外，给 Dahl 盐敏感（SS）大鼠喂食正常盐饮食或 HSE ± 组氨酸，持续 14 天。采用气相色谱 - 质谱联用技术分析肝脏代谢产物。使用 SIMCA - 14.1 分析代谢谱，使用 Gephi - 0.9.2 构建代谢相关网络，并使用 MetaboAnalyst 5.0 在线网站分析通路富集情况。
结果表明，HSE 扰乱了肝脏代谢谱，导致肝脏代谢异常并加剧氧化应激。补充组氨酸可显著逆转肝脏代谢谱。值得注意的是，补充组氨酸后富集了 14 条差异代谢通路，其中大部分在改善氧化还原和一氧化氮（NO）代谢中起重要作用。给予组氨酸可降低过氧化氢和丙二醛水平，并提高抗氧化酶（过氧化氢酶、超氧化物歧化酶、谷胱甘肽 S - 转移酶和谷胱甘肽还原酶）的活性。组氨酸通过增加谷氨酸和半胱氨酸水平有效增强了谷胱甘肽的内源性合成，从而提高了谷胱甘肽系统的抗氧化能力。给予组氨酸后，赖氨酸、谷氨酸和亚牛磺酸在相关网络中具有较高的代谢中心性。此外，组氨酸还可通过增强精氨酸/NO 途径有效增加 NO 的内源性合成。
本研究为组氨酸对肝脏抗氧化保护作用的代谢机制提供了新的见解。
