The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study
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 dis...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/1/284 |
| _version_ | 1797358752644464640 |
|---|---|
| author | Honghui Guo Guang Wang Wei Huang Lingrui Li Yang Bai Haifeng Wang Lina Gao |
| author_facet | Honghui Guo Guang Wang Wei Huang Lingrui Li Yang Bai Haifeng Wang Lina Gao |
| author_sort | Honghui Guo |
| collection | DOAJ |
| description | 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 <i>Staphylococcus aureus</i> 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. |
| first_indexed | 2024-03-08T15:05:40Z |
| format | Article |
| id | doaj.art-c0440d74db354c3e86a8a3267b292770 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:40Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c0440d74db354c3e86a8a3267b2927702024-01-10T14:58:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125128410.3390/ijms25010284The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary StudyHonghui Guo0Guang Wang1Wei Huang2Lingrui Li3Yang Bai4Haifeng Wang5Lina Gao6Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, ChinaDepartment of Laboratory Animal Science, China Medical University, Shenyang 110122, ChinaLiaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, ChinaLiaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, ChinaLiaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, ChinaLiaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, ChinaLiaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, ChinaHepatic 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 <i>Staphylococcus aureus</i> 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.https://www.mdpi.com/1422-0067/25/1/284thioacetamideproteomicsmetabolomicsferroptosishepatic encephalopathy |
| spellingShingle | Honghui Guo Guang Wang Wei Huang Lingrui Li Yang Bai Haifeng Wang Lina Gao The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study International Journal of Molecular Sciences thioacetamide proteomics metabolomics ferroptosis hepatic encephalopathy |
| title | The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study |
| title_full | The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study |
| title_fullStr | The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study |
| title_full_unstemmed | The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study |
| title_short | The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study |
| title_sort | mechanism of hepatic encephalopathy induced by thioacetamide based on metabolomics and proteomics a preliminary study |
| topic | thioacetamide proteomics metabolomics ferroptosis hepatic encephalopathy |
| url | https://www.mdpi.com/1422-0067/25/1/284 |
| work_keys_str_mv | AT honghuiguo themechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT guangwang themechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT weihuang themechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT lingruili themechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT yangbai themechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT haifengwang themechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT linagao themechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT honghuiguo mechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT guangwang mechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT weihuang mechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT lingruili mechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT yangbai mechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT haifengwang mechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy AT linagao mechanismofhepaticencephalopathyinducedbythioacetamidebasedonmetabolomicsandproteomicsapreliminarystudy |