ArticleInternational journal of biological sciences2024
Tenovin-1, a Selective SIRT1/2 Inhibitor, Attenuates High-fat Diet-induced Hepatic Fibrosis via Inhibition of HSC Activation in ZDF Rats.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Integrative Network Pharmacology, Molecular Docking, and In Vitro Insights Into the Mechanism of Finger Citron for Non-Alcoholic Fatty Liver Disease.Food science & nutrition · 2026Article
- Molecular mechanisms of PCSK9 in cardiology: therapeutic implications and clinical impacts on the cardiorenal axis.Molecular and cellular biochemistry · 2026Review
- The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi-target Therapeutic Strategies.Journal of clinical and translational hepatology · 2025Review
- Alterations in Glutathione Redox Homeostasis in Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review.Antioxidants (Basel, Switzerland) · 2024Review
- Sirtuin inhibitors reduce intracellular growth of M. tuberculosis in human macrophages via modulation of host cell immunity.Scientific reports · 2024Article
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Authors and funding
6 authors.
Funding
Abstract
Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-β1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 inhibitor. ZDF rats were divided into chow diet, HFD, and HFD + Tenovin-1 groups. Tenovin-1 reduced hepatic damage, inhibited inflammatory cell infiltration, micro/ macro-vesicular steatosis and prevented collagen deposition HFD-fed rats. Tenovin-1 reduced serum biochemical parameters, triglyceride (TG) and malondialdehyde (MDA) levels but increased glutathione, catalase, and superoxide dismutase levels. Tenovin-1 mitigated proinflammatory cytokines IL-6, IL-1β, TNFα and fibrosis biomarkers in HFD rats, TGF-β1-activated LX-2 and FFA treated SCC cells. Additionally, Tenovin-1 suppressed SIRT1/2 expression and inhibited JNK-1 and STAT3 phosphorylation in HFD rats and FFA-treated SCC cells. In conclusion, Tenovin-1 attenuates hepatic fibrosis by stimulating antioxidants and inhibiting inflammatory cytokines under HFD conditions in diabetic rats.
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