ArticleGut2006
Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats.
Article in Gut, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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Who cites it
30 citing papers in PubMed, 83 citations in OpenAlex.
- MiR-33-5p-opioidergic Signaling Regulates Cognitive Impairment Induced by Bile Duct Ligation in Rats: Ameliorative Role of Naloxone.Brain and behavior · 2025Article
- Targeting the Opioid System in Cardiovascular Disease: Liver Proteomic and Lipid Profile Effects of Naloxone in Atherosclerosis.Biomedicines · 2025Article
- Persistent Transcriptome Alterations in Zebrafish Embryos After Discontinued Opioid Exposure.International journal of molecular sciences · 2025Article
- Nicotine promotes development of bile duct ligation-induced liver fibrosis by increasing expression of nicotinic acetylcholine receptors in rats.Clinical and experimental hepatology · 2024Article
- Exploring the impact of naltrexone on the THBS1/eNOS/NO pathway in osteoporotic bile duct-ligated rats.Scientific reports · 2024Article
- A low dose of naloxone mitigates autoimmune hepatitis by regulating TLR4/NF-κB and Nrf2/HO-1 signaling pathways.Inflammopharmacology · 2023Article
- From liver fibrosis to hepatocarcinogenesis: Role of excessive liver HBioactive materials · 2023Article
- Nanodrug rescues liver fibrosis via synergistic therapy with HCommunications biology · 2023Article
- The synthetic opioid fentanyl increases HIV replication and chemokine co-receptor expression in vitro.Journal of neurovirology · 2022Article
- Review
- Drugs of Abuse and Their Impact on Viral Pathogenesis.Viruses · 2021Review
- Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs.International journal of environmental research and public health · 2021Article
- Article
- Possible involvement of the opioidergic system in the modulation of body temperature, jumping behavior and memory process in cholestatic and addicted mice.EXCLI journal · 2020Article
- Synthetic Opioid Use and Common Injection-associated Viruses: Expanding the Translational Research Agenda.Current HIV research · 2019Review
- A study on OPG/RANK/RANKL axis in osteoporotic bile duct-ligated rats and the involvement of nitrergic and opioidergic systems.Research in pharmaceutical sciences · 2018Article
- Clinical Advancements in the Targeted Therapies against Liver Fibrosis.Mediators of inflammation · 2016Review
- Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update.World journal of gastroenterology · 2014Review
- Current status of novel antifibrotic therapies in patients with chronic liver disease.Therapeutic advances in gastroenterology · 2011Article
- Hepatic stellate cells and astrocytes: Stars of scar formation and tissue repair.Cell cycle (Georgetown, Tex.) · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe aim of this study was to investigate the hypothesis that the opioid system is involved in the development of hepatic fibrosis.
methodsThe effect of naltrexone (an opioid receptor antagonist) on hepatic fibrosis in bile duct ligated (BDL) or sham rats was assessed by histology and hepatic hydroxyproline levels. Liver matrix metalloproteinase 2 (MMP-2) was measured by zymography, and alpha smooth muscle actin (alpha-SMA) and CD45 (leucocyte common antigen) by immunohistochemistry. The redox state of the liver was assessed by hepatic glutathione (GSH)/oxidised glutathione (GSSG) and S-nitrosothiol levels. Subtypes of opioid receptors in cultured hepatic stellate cells (HSCs) were characterised by reverse transcriptase-polymerase chain reaction, and the effects of selective delta opioid receptor agonists on cellular proliferation, tissue inhibitor of metalloproteinase 1 (TIMP-1), and procollagen I expression in HSCs determined.
resultsNaltrexone markedly attenuated the development of hepatic fibrosis as well as MMP-2 activity (p<0.01), and decreased the number of activated HSCs in BDL rats (p<0.05). The development of biliary cirrhosis altered the redox state with a decreased hepatic GSH/GSSG ratio and increased concentrations of hepatic S-nitrosothiols, which were partially or completely normalised by treatment with naltrexone, respectively. Activated rat HSCs exhibited expression of delta1 receptors, with increased procollagen I expression, and increased TIMP-1 expression in response to delta(1) and delta(2) agonists, respectively.
conclusionsThis is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.
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Registered trials
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.