SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model
Intrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of bile acid. There are several crucial generating factors of the pathogenesis of cholestasis, such as inflammation, dysregulation of bile acid transporters and o...
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00256/full |
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| author | Linxi Yu Xiaoxin Liu Zihang Yuan Xiaojiaoyang Li Hang Yang Ziqiao Yuan Lixin Sun Luyong Zhang Luyong Zhang Luyong Zhang Zhengzhou Jiang Zhengzhou Jiang |
| author_facet | Linxi Yu Xiaoxin Liu Zihang Yuan Xiaojiaoyang Li Hang Yang Ziqiao Yuan Lixin Sun Luyong Zhang Luyong Zhang Luyong Zhang Zhengzhou Jiang Zhengzhou Jiang |
| author_sort | Linxi Yu |
| collection | DOAJ |
| description | Intrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of bile acid. There are several crucial generating factors of the pathogenesis of cholestasis, such as inflammation, dysregulation of bile acid transporters and oxidative stress. SIRT1 is regarded as a class III histone deacetylase (HDAC). According to a set of researches, SIRT1 is one of the most important factors which can regulate the hepatic bile acid metabolism. SRT1720 is a kind of activator of SIRT1 which is 1000 times more potent than resveratrol, and this paper is aimed to study its protective influence on hepatotoxicity and cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in mice. The findings revealed that SRT1720 treatment increased FXR and Nrf2 gene expressions to shield against hepatotoxicity and cholestasis induced by ANIT. The mRNA levels of hepatic bile acid transporters were also altered by SRT1720. Furthermore, SRT1720 enhanced the antioxidative system by increasing Nrf2, SOD, GCLc, GCLm, Nqo1, and HO-1 gene expressions. In conclusion, a protective influence could be provided by SRT1720 to cure ANIT-induced hepatotoxicity and cholestasis, which was partly through FXR and Nrf2 activations. These results indicated that SIRT1 could be regarded as a therapeutic target to cure the cholestasis. |
| first_indexed | 2024-12-12T20:31:36Z |
| format | Article |
| id | doaj.art-b0e120fa31bb4f58b34d0f858e243ca8 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T20:31:36Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b0e120fa31bb4f58b34d0f858e243ca82022-12-22T00:13:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-05-01810.3389/fphar.2017.00256235661SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse ModelLinxi Yu0Xiaoxin Liu1Zihang Yuan2Xiaojiaoyang Li3Hang Yang4Ziqiao Yuan5Lixin Sun6Luyong Zhang7Luyong Zhang8Luyong Zhang9Zhengzhou Jiang10Zhengzhou Jiang11Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaJiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical UniversityNanjing, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityNanjing, ChinaJiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University – Ministry of EducationNanjing, ChinaIntrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of bile acid. There are several crucial generating factors of the pathogenesis of cholestasis, such as inflammation, dysregulation of bile acid transporters and oxidative stress. SIRT1 is regarded as a class III histone deacetylase (HDAC). According to a set of researches, SIRT1 is one of the most important factors which can regulate the hepatic bile acid metabolism. SRT1720 is a kind of activator of SIRT1 which is 1000 times more potent than resveratrol, and this paper is aimed to study its protective influence on hepatotoxicity and cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in mice. The findings revealed that SRT1720 treatment increased FXR and Nrf2 gene expressions to shield against hepatotoxicity and cholestasis induced by ANIT. The mRNA levels of hepatic bile acid transporters were also altered by SRT1720. Furthermore, SRT1720 enhanced the antioxidative system by increasing Nrf2, SOD, GCLc, GCLm, Nqo1, and HO-1 gene expressions. In conclusion, a protective influence could be provided by SRT1720 to cure ANIT-induced hepatotoxicity and cholestasis, which was partly through FXR and Nrf2 activations. These results indicated that SIRT1 could be regarded as a therapeutic target to cure the cholestasis.http://journal.frontiersin.org/article/10.3389/fphar.2017.00256/fullSRT1720ANTIcholestasisFXRNrf2 |
| spellingShingle | Linxi Yu Xiaoxin Liu Zihang Yuan Xiaojiaoyang Li Hang Yang Ziqiao Yuan Lixin Sun Luyong Zhang Luyong Zhang Luyong Zhang Zhengzhou Jiang Zhengzhou Jiang SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model Frontiers in Pharmacology SRT1720 ANTI cholestasis FXR Nrf2 |
| title | SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model |
| title_full | SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model |
| title_fullStr | SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model |
| title_full_unstemmed | SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model |
| title_short | SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model |
| title_sort | srt1720 alleviates anit induced cholestasis in a mouse model |
| topic | SRT1720 ANTI cholestasis FXR Nrf2 |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00256/full |
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