ArticlePloS one2013
Simvastatin ameliorates liver fibrosis via mediating nitric oxide synthase in rats with non-alcoholic steatohepatitis-related liver fibrosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05731596 (Comparative Clinical Study to Evaluate the Possible Efficacy and Safety of Rosuvastatin Versus Coenzyme Q10 on Nonalcoholic Steatohepatitis), which is not on this map. Cited by 58 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Comparative Clinical Study to Evaluate the Possible Efficacy and Safety of Rosuvastatin Versus Coenzyme Q10 on Nonalcoholic Steatohepatitis
Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action.Molecules (Basel, Switzerland) · 2024Pooled it
- Statins in Hepatitis B or C Patients Is Associated With Reduced Hepatocellular Carcinoma Risk: A Systematic Review and Meta-Analysis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Pooled it
- Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.World journal of gastroenterology · 2015Trial
- Article
- Unlocking the Hepatoprotective Potential of Urolithin A in High-Fat Diet-Induced MASLD: Integrated Role of Oxidative Stress, Inflammation, FXR/PPAR-α, and Fibrotic Pathway.Cell biochemistry and function · 2026Article
- High-Fat Diet-Induced Morphometric Alterations in the Rat Salivary Glands.European journal of dentistry · 2026Article
- TLR4-Mediated Immune Dysfunction Links MASLD and Parkinson's Disease: Insights from an Omics-Based Network Analysis.NeuroSci · 2026Article
- Triglyceride-lowering therapies for hepatic steatosis: mechanisms, efficacy, and clinical perspectives.Frontiers in pharmacology · 2026Review
- Salutary effects of transdermal curcumin on multiple indices of health span in rodent models of normal aging and hypertension.GeroScience · 2025Article
- Aging-Associated Liver Sinusoidal Endothelial Cells Dysfunction Aggravates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Aging cell · 2025Article
- The prognostic impact of statin exposure in metabolic dysfunction-associated steatotic liver disease: a cohort study.Translational gastroenterology and hepatology · 2025Article
- Impact of statins in the liver: A bane or a boon?Canadian liver journal · 2024Review
- The effects of simvastatin-loaded nanoliposomes on human multilineage liver fibrosis microtissue.Journal of cellular and molecular medicine · 2024Article
- The Interplay between Liver Sinusoidal Endothelial Cells, Platelets, and Neutrophil Extracellular Traps in the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of clinical medicine · 2024Review
- Inflammation drives pathogenesis of early intestinal failure-associated liver disease.Scientific reports · 2024Article
- Immune system dysregulation in the pathogenesis of non-alcoholic steatohepatitis: unveiling the critical role of T and B lymphocytes.Frontiers in immunology · 2024Review
- Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma.Frontiers in pharmacology · 2024Review
- Optimization of Statin-Loaded Delivery Nanoparticles for Treating Chronic Liver Diseases by Targeting Liver Sinusoidal Endothelial Cells.Pharmaceutics · 2023Article
- Biased Quantification of Rat Liver Fibrosis-Meta-Analysis with Practical Recommendations and Clinical Implications.Journal of clinical medicine · 2023Article
- Targeting Endothelial Necroptosis Disrupts Profibrotic Endothelial-Hepatic Stellate Cells Crosstalk to Alleviate Liver Fibrosis in Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSimvastatin exerts pleiotropic effects on cardiovascular system. However, its effect on non-alcoholic fatty liver disease, especially the liver fibrosis, remains obscure. We aimed to clarify the relationship between simvastatin and liver fibrosis both in vivo and in vitro.
methodsA High-fat diet was given to establish rat models with non-alcoholic steatohepatitis (NASH)-related liver fibrosis and simvastatin (4mg·kg(-1)·d(-1)) was administrated intragastrically until hepatic histological findings confirmed the appearance of fibrosis. Human hepatic stellate cell (HSC) line lx-2 cells were cultured in an adipogenic differentiating mixture (ADM) and then were treated with transforming growth factorβ1 (TGF-β1), served as a positive control, simvastatin, TGF-β1 plus simvastatin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, a inhibitor of nitric oxide synthase), and L-NAME plus simvastatin, respectively. The expressions of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and Collagen І as well as cellular α-smooth muscle actin (α-SMA) were measured by real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot in liver tissue and HSC.
resultsWith the progress of NASH-related fibrosis, hepatic mRNA and protein expressions of iNOS, α-SMA, and Collagen І were increased while those of eNOS were decreased. Compared with model rats in 24(th) week group, rats in simvastatin group had less expressions of iNOS, α-SMA, and Collagen І and more expressions of eNOS. In vitro, LX-2 cells acquired quiescent phenotype when cultured in ADM, and TGF-β1 could activate the quiescent HSC. Simvastatin inhibited LX-2 cells activation due to TGF-β1 or L-NAME by increasing the expression of eNOS and decreasing the expression of iNOS.
conclusionsSimvastatin improves the prognosis of NASH-related fibrosis by increasing the expression of eNOS, decreasing the expression of iNOS, and inhibiting the activation of HSC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.