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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wang, Y. Wong, G. T. C. Man, K. Irwin, M. G. |
| Description | Country affiliation: Hong Kong Author Affiliation: Wang Y ( Department of Anaesthesiology, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.) |
| Abstract | BACKGROUND: Opioids have been shown to attenuate ischaemia-reperfusion injury (IRI) in a number of organs. We evaluated the effect of morphine pretreatment on IRI in both normal and cirrhotic rat liver. METHODS: Morphine was administered either i.v. or intrathecally (i.t.) 10 min before initiating 1 h of ischaemia followed by 6 h reperfusion in normal rat liver. Hepatic injury was assessed histologically using Suzuki's criteria. These manoeuvres were repeated using the optimal dose of morphine after administration of naloxone methiodide and wortmannin. Serum levels of transaminases were measured, and expression of phosphorylated Akt, Jak2, and STAT3 were assessed by immunoblotting. Similar procedures were repeated on rats with carbon tetrachloride-induced liver cirrhosis, and the levels of phosphorylated protein kinase C (PKC), haem oxygenase-1 (HO-1), and inducible nitric oxide synthase (iNOS) were also evaluated, as these proteins have beneficial effects during IRI. RESULTS: Morphine pretreatment at 100 µg kg(-1) (i.v.) or 10 µg (i.t.) reduced necrosis, apoptosis, and serum transaminase levels, and increased phosphorylated Akt and STAT3 but not JAK2 expression in normal liver. These changes were reversed by prior administration of naloxone methiodide and wortmannin. Although morphine preconditioning was also protective in cirrhotic liver, STAT3 and JAK2 phosphorylation status was unchanged. There was, however, increased expression of phosphorylated PKC and HO-1, and a reduction in iNOS. CONCLUSIONS: Morphine preconditioning protects against IRI in both normal and cirrhotic rat liver. This involves opioid receptors, phosphatidylinositol-3-kinase, and Akt. The downstream pathways involved are different for cirrhotic liver, with preliminary evidence suggesting involvement of HO-1. |
| File Format | HTM / HTML |
| ISSN | 00070912 |
| e-ISSN | 14716771 |
| Journal | British Journal of Anaesthesia |
| Issue Number | 4 |
| Volume Number | 109 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2012-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Anesthesiology Analgesics, Opioid Therapeutic Use Liver Cirrhosis, Experimental Complications Liver Injuries Morphine Reperfusion Injury Prevention & Control Alanine Transaminase Blood Administration & Dosage Animals Apoptosis Drug Effects Aspartate Aminotransferases Blotting, Western Carbon Tetrachloride Poisoning Therapy Catheterization Heme Oxygenase-1 Biosynthesis In Situ Nick-end Labeling Injections, Intravenous Injections, Spinal Ischemic Preconditioning Pathology Chemically Induced Rats, Sprague-dawley Signal Transduction Comparative Study |
| Content Type | Text |
| Resource Type | Article |
| Subject | Anesthesiology and Pain Medicine |
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