Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis
Glucuronidation catalyzed by UDP-glucuronosyltransferases (UGTs) is one of the most important phase II mechanisms, facilitating drug clearance via conjugation of glucuronic acid with polar groups of xenobiotics. Accumulating evidence suggests that IBDs impact drug disposition, but whether and how IB...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1053610/full |
| _version_ | 1797990015971622912 |
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| author | Wanying Zeng Xiaojing Liu Yangyang Wu Yuting Cai Zhennan Li Fei Ye Yuanhong Sun Feng Li Huijie Xing Shuai Wang |
| author_facet | Wanying Zeng Xiaojing Liu Yangyang Wu Yuting Cai Zhennan Li Fei Ye Yuanhong Sun Feng Li Huijie Xing Shuai Wang |
| author_sort | Wanying Zeng |
| collection | DOAJ |
| description | Glucuronidation catalyzed by UDP-glucuronosyltransferases (UGTs) is one of the most important phase II mechanisms, facilitating drug clearance via conjugation of glucuronic acid with polar groups of xenobiotics. Accumulating evidence suggests that IBDs impact drug disposition, but whether and how IBDs regulate UGTs and drug glucuronidation remains undefined. In this study, we aim to investigate the expression of UGTs and drug glucuronidation in experimental colitis. Given that glucuronidation occurs primarily in the liver, we analyzed the mRNA changes in hepatic UGTs with a DSS-induced mouse colitis model. Twelve UGTs were downregulated in the liver of colitis mice including UGT1A1 and UGT1A9 (two representative UGTs). Colitis in mice downregulated UGT1A1 and UGT1A9 in the liver but not in small intestine, colon, and kidney. We also established that the downregulation of UGTs was attributed to the disease itself rather than the DSS compound. Moreover, colitis-reduced UGT1A1 and UGT1A9 lead to dampened baicalein and puerarin glucuronidation. PXR was the only UGT regulator significantly downregulated in colitis mice, suggesting dysregulation of PXR is associated with the downregulation of UGT1A1 and UGT1A9, thereby potentially resulting in dysfunction of baicalein and puerarin glucuronidation. Collectively, we establish that UGTs and glucuronidation are dysregulated in colitis, and this effect may cause variation in drug responsiveness in IBDs. |
| first_indexed | 2024-04-11T08:28:43Z |
| format | Article |
| id | doaj.art-2ad8e0e68481404a9a4d003e71d6ebc7 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T08:28:43Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-2ad8e0e68481404a9a4d003e71d6ebc72022-12-22T04:34:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10536101053610Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitisWanying Zeng0Xiaojing Liu1Yangyang Wu2Yuting Cai3Zhennan Li4Fei Ye5Yuanhong Sun6Feng Li7Huijie Xing8Shuai Wang9Institute of Molecular Rhythm and Metabolism, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Molecular Rhythm and Metabolism, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInstitute of Molecular Rhythm and Metabolism, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInstitute of Molecular Rhythm and Metabolism, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInstitute of Molecular Rhythm and Metabolism, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInstitute of Molecular Rhythm and Metabolism, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInfectious Diseases Institute, Guangzhou Eighth People’s Hospital, Guangzhou, ChinaInstitution of Laboratory Animal, Jinan University, Guangzhou, ChinaInstitute of Molecular Rhythm and Metabolism, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaGlucuronidation catalyzed by UDP-glucuronosyltransferases (UGTs) is one of the most important phase II mechanisms, facilitating drug clearance via conjugation of glucuronic acid with polar groups of xenobiotics. Accumulating evidence suggests that IBDs impact drug disposition, but whether and how IBDs regulate UGTs and drug glucuronidation remains undefined. In this study, we aim to investigate the expression of UGTs and drug glucuronidation in experimental colitis. Given that glucuronidation occurs primarily in the liver, we analyzed the mRNA changes in hepatic UGTs with a DSS-induced mouse colitis model. Twelve UGTs were downregulated in the liver of colitis mice including UGT1A1 and UGT1A9 (two representative UGTs). Colitis in mice downregulated UGT1A1 and UGT1A9 in the liver but not in small intestine, colon, and kidney. We also established that the downregulation of UGTs was attributed to the disease itself rather than the DSS compound. Moreover, colitis-reduced UGT1A1 and UGT1A9 lead to dampened baicalein and puerarin glucuronidation. PXR was the only UGT regulator significantly downregulated in colitis mice, suggesting dysregulation of PXR is associated with the downregulation of UGT1A1 and UGT1A9, thereby potentially resulting in dysfunction of baicalein and puerarin glucuronidation. Collectively, we establish that UGTs and glucuronidation are dysregulated in colitis, and this effect may cause variation in drug responsiveness in IBDs.https://www.frontiersin.org/articles/10.3389/fphar.2022.1053610/fullUGTs (UDP-glycosyltransferases)glucuronidationcolitisDSSbaicaleinpuerarin |
| spellingShingle | Wanying Zeng Xiaojing Liu Yangyang Wu Yuting Cai Zhennan Li Fei Ye Yuanhong Sun Feng Li Huijie Xing Shuai Wang Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis Frontiers in Pharmacology UGTs (UDP-glycosyltransferases) glucuronidation colitis DSS baicalein puerarin |
| title | Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis |
| title_full | Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis |
| title_fullStr | Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis |
| title_full_unstemmed | Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis |
| title_short | Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis |
| title_sort | dysregulated hepatic udp glucuronosyltransferases and flavonoids glucuronidation in experimental colitis |
| topic | UGTs (UDP-glycosyltransferases) glucuronidation colitis DSS baicalein puerarin |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1053610/full |
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