ArticleGut2007
micro-Opioid receptor activation prevents acute hepatic inflammation and cell death.
Article in Gut, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Gut microbiota dysbiosis and hepatic inflammation in morphine dependence and withdrawal: insights from a rat model.BMC gastroenterology · 2026Article
- Targeting the Opioid System in Cardiovascular Disease: Liver Proteomic and Lipid Profile Effects of Naloxone in Atherosclerosis.Biomedicines · 2025Article
- Fentanyl overdose: Temporal effects and prognostic factors in SKH1 mice.Basic & clinical pharmacology & toxicology · 2024Article
- Hepatic transcript signatures predict atherosclerotic lesion burden prior to a 2-year high cholesterol, high fat diet challenge.PloS one · 2022Article
- Article
- Topical Loperamide-Encapsulated Liposomal Gel Increases the Severity of Inflammation and Accelerates Disease Progression in the Adjuvant-Induced Model of Experimental Rheumatoid Arthritis.Frontiers in pharmacology · 2017Article
- Involvement of Mu Opioid Receptor Signaling in the Protective Effect of Opioid against 6-Hydroxydopamine-Induced SH-SY5Y Human Neuroblastoma Cells Apoptosis.Basic and clinical neuroscience · 2015Article
- Activation of μ opioid receptors modulates inflammation in acute experimental colitis.Neurogastroenterology and motility · 2015Article
- Effect of remifentanil on mitochondrial oxygen consumption of cultured human hepatocytes.PloS one · 2012Article
- Influence of endogenous opioid systems on T lymphocytes as assessed by the knockout of mu, delta and kappa opioid receptors.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2011Article
- Peripheral mechanisms of pain and analgesia.Brain research reviews · 2009Review
- Increased adiposity on normal diet, but decreased susceptibility to diet-induced obesity in mu-opioid receptor-deficient mice.European journal of pharmacology · 2008Article
- The effects of tramadol on hepatic ischemia/reperfusion injury in rats.Indian journal of pharmacologyArticle
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsThe detrimental impact of opioid agonist on the clinical management of inflammatory diseases remains elusive. Given the anti-inflammatory properties of the mu-opioid receptor (MOR) agonists at the intestinal barrier, we hypothesised that MOR activation might also dampen acute hepatic inflammation and cell death-major determinants in the pathogenesis of liver diseases. PATIENTS AND
methodsThe expression of MOR in liver biopsy specimens and peripheral blood mononuclear cells of untreated patients with chronic hepatitis C virus infection and controls, primary hepatocytes and cell lines was determined by quantitative PCR, immunoblotting and/or immunohistochemistry. The effects of peripheral MOR agonist (d-Ala2,NMe-Phe4,Gly5-ol (DAMGO)) and/or antagonist (naloxone methiodide) were explored in two models of acute hepatitis in mice. MOR-deficient mice were used to evaluate the essential regulatory role of MOR during carbon tetrachloride (CCl(4))-induced hepatitis. The role of DAMGO in cell death was investigated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) analysis and quantification of lactate dehydrogenase release.
resultsThe key role of MOR in the prevention of acute hepatic inflammation and cell death in vivo and in vitro is reported. Whereas MOR gene expression increased transiently in the model of acute liver injury and TNFalpha-treated HepG2 cells, an impaired expression of MOR mRNA in human chronic hepatitis C samples was found. Furthermore, preventive administration of the selective MOR agonist DAMGO enhanced hepatoprotective-signalling pathways in vivo that were blocked by using naloxone methiodide. Consistently, genetic and pharmacological inhibition of MOR enhanced the severity associated with experimental hepatotoxin-induced hepatitis. Finally, treatment with DAMGO was shown to prevent cell death in vitro in HepG2 cells in a MOR-dependent manner and to prevent concanavalin A- and CCl(4)-induced cell death in vivo, providing a possible explanation for the anti-inflammatory role of MOR activation in the liver.
conclusionsThe results indicate that MOR agonists may prevent acute hepatitis and hold promising therapeutic use to maintain remission in both chronic inflammatory bowel and liver diseases.
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