ArticleNaunyn-Schmiedeberg's archives of pharmacology2015
The multi-kinase inhibitor pazopanib targets hepatic stellate cell activation and apoptosis alleviating progression of liver fibrosis.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- Enhanced mitigation of diabetic myocardial injury in rats via modulating the adiponectin/IRS-1/PI3K/p-AKT/FOXO-1 signaling by combining methotrexate and insulin.Molecular biology reports · 2026Article
- A Proteomics Resource Investigating Fibrosis: Proof-of-Concept for Identifying Novel Drug Candidates.Proteomics · 2026Article
- Citrus Essential Oil Nanoemulsions Mitigate Cardiac, Hepatic, and Pancreatic Injury in High-Fat Obese Rats via Adiponectin/SIRT1/Nrf2 Signaling Pathways.Journal of nutrition and metabolism · 2026Article
- Targeting JNK1/2 and P38 Mitogen-Activated Protein Kinases With Pazopanib Mitigates Bleomycin-Induced Lung Fibrosis.Archiv der Pharmazie · 2025Article
- The AURKA-Selective Inhibitor Alisertib Attenuates Doxorubicin-Induced Hepatotoxicity in Mice via Modulation of IL-17A/NF-κB and STAT3 Signaling Pathways.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Cognitive enhancing effects of pazopanib in D‑galactose/ovariectomized Alzheimer's rat model: insights into the role of RIPK1/RIPK3/MLKL necroptosis signaling pathway.Inflammopharmacology · 2023Article
- Repurposing of Kinase Inhibitors for Treatment of COVID-19.Pharmaceutical research · 2020Review
- Easy-to-use strategy for reference gene selection in quantitative real-time PCR experiments.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase inhibitors have been emerged recently as an effective therapy against liver fibrosis. The current study was designed to test a potential anti-fibrotic effect of the multi-targeted receptor tyrosine kinase inhibitor pazopanib. Carbon tetrachloride (CCl4; 1 mL/kg) was injected intraperitoneally (i.p.) twice/week for 8 weeks. Pazopanib (10 and 30 mg/kg, i.p.) was administered three times/week at the beginning of week 5. Levels of liver function biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, and total bilirubin), malondialdehyde, transforming growth factor-β1 (TGF-β1), caspase-3, factor-related apoptosis (FAS), vascular endothelial growth factor (VEGF) receptor-1, and pigment endothelial derived factor (PEDF) were measured. The tissue level of the inflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α) were assigned. Fibrotic area was measured by morphometry and expression of alpha-smooth muscle actin (α-SMA), caspase-3, platelet-derived growth factor (PDGF) receptor-β, and matrix metalloproteinase-2 (MMP-2) was scored immunohistochemically. Hepatic expression of collagen-1-alpha-1 (Col1A1) and tissue inhibitor metalloproteinase-1 (TIMP-1) mRNA were assigned by RT-qPCR. Injection of CCl4 resulted in marked collagen deposition, necroinflammation, and fibrosis (2.67%). Pazopanib in a dose of 30 mg/kg improved liver function, reduced fibrosis (1.48%), and decreased significantly (P < 0.01) liver expression of malondialdehyde, TGF-β1, IL-6, TNF-α, Col1A1, TIMP-1, α-SMA, MMP-2, PDGF receptor-β, and VEGF receptor-1. Additionally, the apoptotic markers (caspase-3, FAS) and the anti-angiogenic factor PEDF were upregulated significantly (P < 0.05). Pazopanib at a certain dose level can halt liver fibrosis progression through modulating inflammatory cytokines, suppressing stellate cell activity, inducing apoptosis, and potentially regulating angiogenesis.
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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.