Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets
Acute pancreatitis (AP), induced by tetracycline, a widely used antibiotic, poses significant clinical and toxicological challenges, yet its molecular mechanisms remain unclear. This study aims to promote drug toxicology strategies for the effective investigation of the putative toxicity and potenti...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Toxics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6304/12/12/929 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846102596311318528 |
|---|---|
| author | Hang Lei Yimao Wu Wenjun Ma Jiaqi Yao Pengcheng Zhang Yong Tian Yuhong Jiang Zhijun Xie Lv Zhu Wenfu Tang |
| author_facet | Hang Lei Yimao Wu Wenjun Ma Jiaqi Yao Pengcheng Zhang Yong Tian Yuhong Jiang Zhijun Xie Lv Zhu Wenfu Tang |
| author_sort | Hang Lei |
| collection | DOAJ |
| description | Acute pancreatitis (AP), induced by tetracycline, a widely used antibiotic, poses significant clinical and toxicological challenges, yet its molecular mechanisms remain unclear. This study aims to promote drug toxicology strategies for the effective investigation of the putative toxicity and potential molecular mechanisms of antibiotic drugs through the study of tetracycline in AP. Using the SwissTargetPrediction, SEA Search, Super-PRED, GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD), we identified 259 potential targets associated with tetracycline exposure and AP. Further refinement via the STRING database and Cytoscape (version 3.10.1) software highlighted 22 core targets, including TP53, TNF, and AKT1. Functional enrichment via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) identified pathways through Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, highlighting PI3K-Akt, MAPK, HIF-1, and AGE-RAGE as critical mediators in tetracycline-induced AP. Molecular docking confirmed the strong binding between tetracycline and the core targets. Overall, these findings suggest that tetracycline may affect the occurrence and progression of pancreas-related inflammation by regulating pancreatic cell apoptosis and proliferation, activating inflammatory signaling pathways, and regulating lipid metabolic pathways. This study provides a theoretical basis for understanding the molecular mechanism of tetracycline-induced AP and lays the foundation for the prevention and treatment of digestive system diseases associated with excessive exposure to tetracycline antibiotics and certain tetracyclines. In addition, our network toxicology approach has accelerated the elucidation of toxic pathways in antibiotic drugs that lack specific characteristics. |
| format | Article |
| id | doaj-art-c720d669a5d44cd2a7ec1ac0029cf0df |
| institution | Kabale University |
| issn | 2305-6304 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj-art-c720d669a5d44cd2a7ec1ac0029cf0df2024-12-27T14:56:49ZengMDPI AGToxics2305-63042024-12-01121292910.3390/toxics12120929Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and TargetsHang Lei0Yimao Wu1Wenjun Ma2Jiaqi Yao3Pengcheng Zhang4Yong Tian5Yuhong Jiang6Zhijun Xie7Lv Zhu8Wenfu Tang9West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaSecond Clinical Medical College, Guangdong Medical University, Dongguan 523808, ChinaStomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing 401147, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaAcute pancreatitis (AP), induced by tetracycline, a widely used antibiotic, poses significant clinical and toxicological challenges, yet its molecular mechanisms remain unclear. This study aims to promote drug toxicology strategies for the effective investigation of the putative toxicity and potential molecular mechanisms of antibiotic drugs through the study of tetracycline in AP. Using the SwissTargetPrediction, SEA Search, Super-PRED, GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD), we identified 259 potential targets associated with tetracycline exposure and AP. Further refinement via the STRING database and Cytoscape (version 3.10.1) software highlighted 22 core targets, including TP53, TNF, and AKT1. Functional enrichment via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) identified pathways through Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, highlighting PI3K-Akt, MAPK, HIF-1, and AGE-RAGE as critical mediators in tetracycline-induced AP. Molecular docking confirmed the strong binding between tetracycline and the core targets. Overall, these findings suggest that tetracycline may affect the occurrence and progression of pancreas-related inflammation by regulating pancreatic cell apoptosis and proliferation, activating inflammatory signaling pathways, and regulating lipid metabolic pathways. This study provides a theoretical basis for understanding the molecular mechanism of tetracycline-induced AP and lays the foundation for the prevention and treatment of digestive system diseases associated with excessive exposure to tetracycline antibiotics and certain tetracyclines. In addition, our network toxicology approach has accelerated the elucidation of toxic pathways in antibiotic drugs that lack specific characteristics.https://www.mdpi.com/2305-6304/12/12/929tetracyclineacute pancreatitisnetwork toxicologymolecular dockingtoxicant metabolism |
| spellingShingle | Hang Lei Yimao Wu Wenjun Ma Jiaqi Yao Pengcheng Zhang Yong Tian Yuhong Jiang Zhijun Xie Lv Zhu Wenfu Tang Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets Toxics tetracycline acute pancreatitis network toxicology molecular docking toxicant metabolism |
| title | Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets |
| title_full | Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets |
| title_fullStr | Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets |
| title_full_unstemmed | Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets |
| title_short | Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets |
| title_sort | network toxicology and molecular docking analysis of tetracycline induced acute pancreatitis unveiling core mechanisms and targets |
| topic | tetracycline acute pancreatitis network toxicology molecular docking toxicant metabolism |
| url | https://www.mdpi.com/2305-6304/12/12/929 |
| work_keys_str_mv | AT hanglei networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT yimaowu networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT wenjunma networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT jiaqiyao networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT pengchengzhang networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT yongtian networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT yuhongjiang networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT zhijunxie networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT lvzhu networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets AT wenfutang networktoxicologyandmoleculardockinganalysisoftetracyclineinducedacutepancreatitisunveilingcoremechanismsandtargets |