The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study

被引:3
|
作者
Guo, Honghui [1 ,2 ,3 ]
Wang, Guang [4 ]
Huang, Wei [1 ,2 ,3 ]
Li, Lingrui [1 ,2 ,3 ]
Bai, Yang [1 ,2 ,3 ]
Wang, Haifeng [1 ,2 ,3 ]
Gao, Lina [1 ,2 ,3 ]
机构
[1] Liaoning Prov Key Lab Forens Bioevidence Sci, Shenyang 110122, Peoples R China
[2] China Med Univ Ctr Forens Invest, Shenyang 110122, Peoples R China
[3] China Med Univ, Dept Forens Analyt Toxicol, Shenyang 110122, Peoples R China
[4] China Med Univ, Dept Lab Anim Sci, Shenyang 110122, Peoples R China
关键词
thioacetamide; proteomics; metabolomics; ferroptosis; hepatic encephalopathy; RANDOMIZED CONTROLLED-TRIAL; NEUROSTEROIDS; IMPAIRMENT; LACTULOSE; AMMONIA; MODEL; RATS;
D O I
10.3390/ijms25010284
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatic encephalopathy (HE) is a central nervous system dysfunction syndrome caused by acute and chronic liver failure or various portal systemic shunt disorders. HE arises from metabolic disorder and excludes other known types of encephalopathy. HE is a major cause of death in people with liver disease. Early diagnosis and timely treatment are key to improving HE prognosis. Herein, we established a model of HE and performed metabolomics to identify 50 significantly differential metabolites between the HE group and control group. The main metabolic pathways associated with these differential metabolites were the purine metabolism, pyrimidine metabolism, aminoacyl tRNA biosynthesis, and glucose metabolism. Through proteomics analysis, we identified 226 significantly differential proteins (52 up-regulated and 174 down-regulated). The main (Kyoto Encyclopedia of Genes and Genomes) enrichment pathways were the Staphylococcus aureus infection, vitamin digestion and absorption, and complement and coagulation cascades. Through the conjoint analysis of proteomics and metabolomics, the differentially present proteins and metabolites were found to be involved in vitamin digestion and absorption, and ferroptosis pathways. In HE, malondialdehyde was significantly elevated, but glutathione was significantly diminished, and the redox balance was destroyed, thus leading to changes in proteins' levels associated with the ferroptosis pathway. In conclusion, this study preliminarily explored the molecular and metabolic mechanisms underlying HE.
引用
收藏
页数:22
相关论文
共 50 条
  • [21] Integrated Proteomics and Metabolomics Reveal the Mechanism of Nephrotoxicity Induced by Triptolide
    Xie, Lijuan
    Zhao, Yiwei
    Duan, Jingyi
    Fan, Simiao
    Shu, Lexin
    Liu, Hui
    Wang, Yuming
    Xu, Yanyan
    Li, Yubo
    CHEMICAL RESEARCH IN TOXICOLOGY, 2020, 33 (07) : 1897 - 1906
  • [22] Thioacetamide-induced acute hepatic encephalopathy: central vs peripheral effect of Allicin
    Dalia O. Saleh
    Dina F. Mansour
    Ahmed M. Fayez
    Metabolic Brain Disease, 2021, 36 : 1331 - 1340
  • [23] Effects of caffeic acid phenethyl ester on thioacetamide-induced hepatic encephalopathy in rats
    Fadillioglu, Ersin
    Gursul, Cebrail
    Iraz, Mustafa
    PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2010, 34 (08): : 1440 - 1445
  • [24] Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice
    Avraham, Y
    Israeli, E
    Gabbay, E
    Okun, A
    Zolotarev, O
    Silberman, I
    Ganzburg, V
    Dagon, Y
    Magen, I
    Vorobia, L
    Pappo, O
    Mechoulam, R
    Ilan, Y
    Berry, EM
    NEUROBIOLOGY OF DISEASE, 2006, 21 (01) : 237 - 245
  • [25] The Changes of Mitochondria in Substantia Nigra and Anterior Cerebral Cortex of Hepatic Encephalopathy Induced by Thioacetamide
    Bai, Yunhu
    Wang, Shengming
    Wu, Feifei
    Xie, Xiangjun
    Wang, Yayun
    Yang, Yanling
    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, 2019, 302 (07): : 1169 - 1177
  • [26] Thioacetamide-induced acute hepatic encephalopathy: central vs peripheral effect of Allicin
    Saleh, Dalia O.
    Mansour, Dina F.
    Fayez, Ahmed M.
    METABOLIC BRAIN DISEASE, 2021, 36 (06) : 1331 - 1340
  • [27] Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure
    Chu, CJ
    Wang, SS
    Lee, FY
    Chang, FY
    Lin, HC
    Hou, MC
    Chan, CC
    Wu, SL
    Chen, CT
    Huang, HC
    Lee, SD
    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2001, 31 (02) : 156 - 163
  • [28] Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure
    Chu, Chi-Jen
    Hsiao, Ching-Chin
    Wang, Teh-Fang
    Chan, Cho-Yu
    Lee, Fa-Yauh
    Chang, Full-Young
    Chen, Yi-Chou
    Huang, Hui-Chun
    Wang, Sun-Sang
    Lee, Shou-Dong
    WORLD JOURNAL OF GASTROENTEROLOGY, 2005, 11 (02) : 232 - 236
  • [29] Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure
    Chi-Jen Chu
    Ching-Chin Hsiao
    Teh-Fang Wang
    Cho-Yu Chan
    Fa-Yauh Lee
    Full-Young Chang
    Shou-Dong Lee
    World Journal of Gastroenterology, 2005, (02) : 232 - 236
  • [30] A pilot study of the onset of hepatic encephalopathy (OHE) in mice induced by thioacetamide and the protective effect of taurine by holistic metabolic characterization
    Dan-Dan Wei
    Jun-Song Wang
    Ming-Hui Li
    Ping-Ping Guo
    Ge Dong
    Ming-Hua Yang
    Ling-Yi Kong
    Metabolomics, 2015, 11 : 559 - 570