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SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model
Linxi Yu1, Xiaoxin Liu1, Zihang Yuan1
1Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical UniversityNanjing, China.
Frontiers in Pharmacology
|May 30, 2017
Summary
SRT1720, a SIRT1 activator, protected mice from liver injury and bile acid buildup caused by ANIT. This compound enhanced protective gene expressions, suggesting SIRT1 as a therapeutic target for cholestasis.
Area of Science:
- Hepatology
- Biochemistry
- Pharmacology
Background:
- Intrahepatic cholestasis involves bile acid accumulation and hepatotoxicity, driven by inflammation, transporter dysregulation, and oxidative stress.
- Sirtuin 1 (SIRT1), a class III histone deacetylase, plays a key role in regulating hepatic bile acid metabolism.
Purpose of the Study:
- To investigate the protective effects of SRT1720, a potent SIRT1 activator, against alpha-naphthylisothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in mice.
Main Methods:
- Mice were treated with ANIT to induce cholestasis and hepatotoxicity, followed by administration of SRT1720.
- Gene expression levels of key metabolic regulators (FXR, Nrf2) and antioxidant enzymes were analyzed.
Main Results:
- SRT1720 treatment significantly reduced ANIT-induced hepatotoxicity and cholestasis.
- SRT1720 upregulated the expression of FXR and Nrf2, crucial for combating liver injury.
- The activator enhanced the antioxidative system by increasing Nrf2, SOD, GCLc, GCLm, Nqo1, and HO-1 gene expressions.
Conclusions:
- SRT1720 demonstrates a protective effect against ANIT-induced liver injury and cholestasis in mice.
- These protective effects are partly mediated through the activation of FXR and Nrf2 pathways.
- SIRT1 represents a potential therapeutic target for managing cholestatic liver diseases.
