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Article: Pretreatment with intrathecal or intravenous morphine attenuates hepatic ischaemia-reperfusion injury in normal and cirrhotic rat liver

TitlePretreatment with intrathecal or intravenous morphine attenuates hepatic ischaemia-reperfusion injury in normal and cirrhotic rat liver
Authors
KeywordsCirrhosis
Damage
Hepatic ischaemiareperfusion injury
Intrathecal morphine
Liver
Issue Date2012
PublisherOxford University Press. The Journal's web site is located at http://bja.oxfordjournals.org/
Citation
British Journal of Anaesthesia, 2012, v. 109 n. 4, p. 529-539 How to Cite?
AbstractBackground 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. liver, with preliminary evidence suggesting involvement of HO-1.
Persistent Identifierhttp://hdl.handle.net/10722/159237
ISSN
2015 Impact Factor: 5.616
2015 SCImago Journal Rankings: 2.314
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Yen_US
dc.contributor.authorWong, GTCen_US
dc.contributor.authorMan, Ken_US
dc.contributor.authorIrwin, MGen_US
dc.date.accessioned2012-08-16T05:47:06Z-
dc.date.available2012-08-16T05:47:06Z-
dc.date.issued2012en_US
dc.identifier.citationBritish Journal of Anaesthesia, 2012, v. 109 n. 4, p. 529-539en_US
dc.identifier.issn0007-0912-
dc.identifier.urihttp://hdl.handle.net/10722/159237-
dc.description.abstractBackground 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. liver, with preliminary evidence suggesting involvement of HO-1.-
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://bja.oxfordjournals.org/-
dc.relation.ispartofBritish Journal of Anaesthesiaen_US
dc.subjectCirrhosis-
dc.subjectDamage-
dc.subjectHepatic ischaemiareperfusion injury-
dc.subjectIntrathecal morphine-
dc.subjectLiver-
dc.titlePretreatment with intrathecal or intravenous morphine attenuates hepatic ischaemia-reperfusion injury in normal and cirrhotic rat liveren_US
dc.typeArticleen_US
dc.identifier.emailWong, GTC: gordon@hku.hken_US
dc.identifier.emailMan, K: kwanman@hku.hken_US
dc.identifier.emailIrwin, MG: mgirwin@hku.hken_US
dc.identifier.authorityWong, GTC=rp00523en_US
dc.identifier.authorityMan, K=rp00417en_US
dc.identifier.authorityIrwin, MG=rp00390en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/bja/aes209-
dc.identifier.pmid22745352-
dc.identifier.scopuseid_2-s2.0-84866362598-
dc.identifier.hkuros202217en_US
dc.identifier.volume109-
dc.identifier.issue4-
dc.identifier.spage529-
dc.identifier.epage539-
dc.identifier.eissn1471-6771-
dc.identifier.isiWOS:000308886700008-
dc.publisher.placeUnited Kingdom-

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