Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors
Aristolochic acids (AAs) represent a class of nitrophenanthrene carboxylic acids naturally existing or accidentally mixed in herbal medicines or crops, which have long been recognized for causing nephropathy. Recently, the linkage between AAs and liver injury has become a concern; however, the curre...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-11-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324013423 |
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| author | Yumei Ma Chenlong Du Yuzhen Liu Meiyao Feng Yingqing Shou Dianke Yu Yuan Jin |
| author_facet | Yumei Ma Chenlong Du Yuzhen Liu Meiyao Feng Yingqing Shou Dianke Yu Yuan Jin |
| author_sort | Yumei Ma |
| collection | DOAJ |
| description | Aristolochic acids (AAs) represent a class of nitrophenanthrene carboxylic acids naturally existing or accidentally mixed in herbal medicines or crops, which have long been recognized for causing nephropathy. Recently, the linkage between AAs and liver injury has become a concern; however, the current understanding of the mechanism or mode of action (MOA) is limited. In the present study, we investigated nuclear receptor-mediated MOA associated with AAs-induced liver injury including dyslipidemia and hepatotoxicity. Bioinformatic analysis of AAI-interacting genes indicated nuclear receptor-mediated metabolizing pathways; Transcriptomic profiling of AAs-exposed rats with liver injury suggested FXR-, NRF2-, and AHR- mediated pathways in the injured livers of the rats. Mechanistic investigation using HepG2 cells indicated AAI-induced hepatic lipid accumulation by elevating Triglyceride (TG) through inhibition of the FXR. In addition, AAI-induced hepatocellular damage by activating the AHR pathway, which further generated ROS and activated the NRF2 pathway. Together, these results provided new clues for researchers who are interested in chemical-induced liver injury. |
| format | Article |
| id | doaj-art-89ea05c1d0ec4dacb4d85225511c04c3 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-89ea05c1d0ec4dacb4d85225511c04c32024-11-21T06:01:58ZengElsevierEcotoxicology and Environmental Safety0147-65132024-11-01287117266Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptorsYumei Ma0Chenlong Du1Yuzhen Liu2Meiyao Feng3Yingqing Shou4Dianke Yu5Yuan Jin6School of Public Health, Qingdao University, Qingdao, ChinaNingxia Hui Autonomous Region Center for Disease Control and Prevention, Yinchuan, ChinaGaomi Municipal Center for Disease Control and Prevention, Weifang Institute of Preventive Medicine, Weifang, ChinaDepartment of Environmental Health, Qingdao Municipal Center for Disease Control and Prevention, Qingdao Institute of Preventive Medicine, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, China; Correspondence to: School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, Shandong 266021, China.Aristolochic acids (AAs) represent a class of nitrophenanthrene carboxylic acids naturally existing or accidentally mixed in herbal medicines or crops, which have long been recognized for causing nephropathy. Recently, the linkage between AAs and liver injury has become a concern; however, the current understanding of the mechanism or mode of action (MOA) is limited. In the present study, we investigated nuclear receptor-mediated MOA associated with AAs-induced liver injury including dyslipidemia and hepatotoxicity. Bioinformatic analysis of AAI-interacting genes indicated nuclear receptor-mediated metabolizing pathways; Transcriptomic profiling of AAs-exposed rats with liver injury suggested FXR-, NRF2-, and AHR- mediated pathways in the injured livers of the rats. Mechanistic investigation using HepG2 cells indicated AAI-induced hepatic lipid accumulation by elevating Triglyceride (TG) through inhibition of the FXR. In addition, AAI-induced hepatocellular damage by activating the AHR pathway, which further generated ROS and activated the NRF2 pathway. Together, these results provided new clues for researchers who are interested in chemical-induced liver injury.http://www.sciencedirect.com/science/article/pii/S0147651324013423Aristolochic acidsmode of action (MOA)chemical-induced liver injury (CILI)FXRAHR |
| spellingShingle | Yumei Ma Chenlong Du Yuzhen Liu Meiyao Feng Yingqing Shou Dianke Yu Yuan Jin Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors Ecotoxicology and Environmental Safety Aristolochic acids mode of action (MOA) chemical-induced liver injury (CILI) FXR AHR |
| title | Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors |
| title_full | Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors |
| title_fullStr | Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors |
| title_full_unstemmed | Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors |
| title_short | Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors |
| title_sort | aristolochic acid induced dyslipidemia and hepatotoxicity the potential role of fxr and ahr receptors |
| topic | Aristolochic acids mode of action (MOA) chemical-induced liver injury (CILI) FXR AHR |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324013423 |
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