Related Experiment Video
Updated: Nov 15, 2025
Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
The sirtuin 1 activator SRT1720 alleviated endotoxin-induced fulminant hepatitis in mice
Dan Zhou1, Feng Yang2, Ling Lin3,4
1Department of Pathology, Fuling Central Hospital, 2 Gaosuntang Road, Chongqing 408099, P.R. China.
Abstract:
The metabolic sensor sirtuin 1 (SIRT1) also functions as a checkpoint in inflammation, and SRT1720 is a highly active and selective SIRT1 activator shown to alleviate inflammatory injury in several recent experimental studies. In the present study, the potential effects and underlying mechanisms of SRT1720 on lipopolysaccharide (LPS)-induced fulminant hepatitis in D-galactosamine (D-Gal)-sensitized mice were investigated. The results indicated that treatment with SRT1720 inhibited LPS/D-Gal-induced elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated the histological abnormalities, suppressed the induction of tumor necrosis factor alpha (TNF-α) and IL-6, mitigated the phosphorylation of c-Jun N-terminal kinase (JNK), downregulated the activities of caspase 8, caspase 9 and caspase 3, decreased the level of cleaved caspase 3, reduced the TUNEL-positive cells, and improved the survival rate of the LPS/D-Gal-exposed mice. These data indicated that treatment with the SIRT1 activator SRT1720 alleviated LPS/D-Gal-induced fulminant hepatitis, which might be attributed to the suppressive effects of SRT1720 on TNF-α production and the subsequent activation of the apoptosis cascade.
Insights
The SIRT1 activator SRT1720 significantly reduced liver injury and improved survival in a mouse model of fulminant hepatitis. This protection is linked to reduced inflammation and apoptosis.
Area of Science:
- Biochemistry
- Immunology
- Hepatology
Background:
- Sirtuin 1 (SIRT1) is a metabolic sensor involved in inflammation regulation.
- SRT1720 is a potent and selective SIRT1 activator with demonstrated anti-inflammatory effects.
- Fulminant hepatitis is a severe liver condition often triggered by toxins or infections.
Purpose of the Study:
- To investigate the therapeutic potential of SRT1720 in a mouse model of D-galactosamine (D-Gal) and lipopolysaccharide (LPS)-induced fulminant hepatitis.
- To elucidate the underlying mechanisms by which SRT1720 exerts its protective effects.
Main Methods:
- Mice were sensitized with D-Gal and challenged with LPS to induce fulminant hepatitis.
- SRT1720 treatment was administered to assess its impact on liver injury markers and inflammatory responses.
- Key molecular pathways including apoptosis and inflammatory cytokine production were analyzed.
Main Results:
- SRT1720 treatment significantly reduced liver enzyme levels (ALT, AST) and histological damage.
- SRT1720 suppressed the induction of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-6.
- SRT1720 mitigated apoptosis by inhibiting caspase activation and reducing TUNEL-positive cells, leading to improved survival rates.
Conclusions:
- SRT1720 effectively alleviates D-Gal/LPS-induced fulminant hepatitis in mice.
- The protective mechanism involves suppressing TNF-α production and inhibiting the apoptosis cascade.
- SRT1720 represents a potential therapeutic agent for severe inflammatory liver injury.
