Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption
Studies increasingly show that ulcerative colitis (UC) is a consequence of an imbalance between oxidative stress and antioxidant capacity. Bilirubin exerts an anti-inflammatory effect by scavenging reactive oxygen species (ROS), although the exact mechanism is not completely understood. The aim of t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.654808/full |
| _version_ | 1818923237752438784 |
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| author | Chong Zhao Chong Zhao Chong Zhao Hongli Huang Hongli Huang Qiuhua Pan Qiuhua Pan Wenqi Huang Wenqi Huang Wu Peng Wu Peng Haoming Xu Haoming Xu Zhiqiang Feng Zhiqiang Feng Yanlei Du Yanlei Du Yuqiang Nie Yuqiang Nie Yongjian Zhou Yongjian Zhou |
| author_facet | Chong Zhao Chong Zhao Chong Zhao Hongli Huang Hongli Huang Qiuhua Pan Qiuhua Pan Wenqi Huang Wenqi Huang Wu Peng Wu Peng Haoming Xu Haoming Xu Zhiqiang Feng Zhiqiang Feng Yanlei Du Yanlei Du Yuqiang Nie Yuqiang Nie Yongjian Zhou Yongjian Zhou |
| author_sort | Chong Zhao |
| collection | DOAJ |
| description | Studies increasingly show that ulcerative colitis (UC) is a consequence of an imbalance between oxidative stress and antioxidant capacity. Bilirubin exerts an anti-inflammatory effect by scavenging reactive oxygen species (ROS), although the exact mechanism is not completely understood. The aim of this study was to determine the role of serum bilirubin in UC using patient data and a mouse model of dextran sodium sulfate (DSS)-induced colitis. We found that low levels of serum bilirubin correlated to a higher risk of UC in a retrospective case-control population. Pre-treatment with exogenous unconjugated bilirubin (UCB) significantly enhanced colonic bilirubin absorption in mice, and attenuated the DSS-induced body weight loss, colon shortening and histopathological damage. Mechanistically, bilirubin prevented the infiltration of inflammatory cells, and decreased the levels of myeloperoxidase and pro-inflammatory cytokines in the serum and colon. Moreover, bilirubin inhibited ROS and malondialdehyde production, scavenged superoxide anions (O2·−) from the colon and enhanced the total antioxidant capacity. In conclusion, exogenous UCB attenuated DSS-induced colitis by directly scavenging O2·− and enhancing bilirubin reabsorption in the colon via enterohepatic cycling. |
| first_indexed | 2024-12-20T02:06:15Z |
| format | Article |
| id | doaj.art-04868be23ef2429680bb1ae51f9f773f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T02:06:15Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-04868be23ef2429680bb1ae51f9f773f2022-12-21T19:57:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.654808654808Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin ReabsorptionChong Zhao0Chong Zhao1Chong Zhao2Hongli Huang3Hongli Huang4Qiuhua Pan5Qiuhua Pan6Wenqi Huang7Wenqi Huang8Wu Peng9Wu Peng10Haoming Xu11Haoming Xu12Zhiqiang Feng13Zhiqiang Feng14Yanlei Du15Yanlei Du16Yuqiang Nie17Yuqiang Nie18Yongjian Zhou19Yongjian Zhou20Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaGuangzhou Key Laboratory of Digestive Disease, Guangzhou First People’s Hospital, Guangzhou, ChinaStudies increasingly show that ulcerative colitis (UC) is a consequence of an imbalance between oxidative stress and antioxidant capacity. Bilirubin exerts an anti-inflammatory effect by scavenging reactive oxygen species (ROS), although the exact mechanism is not completely understood. The aim of this study was to determine the role of serum bilirubin in UC using patient data and a mouse model of dextran sodium sulfate (DSS)-induced colitis. We found that low levels of serum bilirubin correlated to a higher risk of UC in a retrospective case-control population. Pre-treatment with exogenous unconjugated bilirubin (UCB) significantly enhanced colonic bilirubin absorption in mice, and attenuated the DSS-induced body weight loss, colon shortening and histopathological damage. Mechanistically, bilirubin prevented the infiltration of inflammatory cells, and decreased the levels of myeloperoxidase and pro-inflammatory cytokines in the serum and colon. Moreover, bilirubin inhibited ROS and malondialdehyde production, scavenged superoxide anions (O2·−) from the colon and enhanced the total antioxidant capacity. In conclusion, exogenous UCB attenuated DSS-induced colitis by directly scavenging O2·− and enhancing bilirubin reabsorption in the colon via enterohepatic cycling.https://www.frontiersin.org/articles/10.3389/fphar.2021.654808/fullulcerative colitisbilirubinantioxidantenterohepatic cyclingsuperoxide (O2·−) |
| spellingShingle | Chong Zhao Chong Zhao Chong Zhao Hongli Huang Hongli Huang Qiuhua Pan Qiuhua Pan Wenqi Huang Wenqi Huang Wu Peng Wu Peng Haoming Xu Haoming Xu Zhiqiang Feng Zhiqiang Feng Yanlei Du Yanlei Du Yuqiang Nie Yuqiang Nie Yongjian Zhou Yongjian Zhou Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption Frontiers in Pharmacology ulcerative colitis bilirubin antioxidant enterohepatic cycling superoxide (O2·−) |
| title | Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption |
| title_full | Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption |
| title_fullStr | Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption |
| title_full_unstemmed | Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption |
| title_short | Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption |
| title_sort | unconjugated bilirubin attenuates dss induced colitis potentially via enhancement of bilirubin reabsorption |
| topic | ulcerative colitis bilirubin antioxidant enterohepatic cycling superoxide (O2·−) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.654808/full |
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