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

Abstract

† Opioid preconditioning protects against ischaemia -reperfusion injury (IRI) in many organs. † Morphine given i.v. or intrathecally protected against IRI in both normal and cirrhotic rat liver. † This effect required peripheral m-opioid receptor activation and multiple prosurvival intracellular signalling pathways. † Further studies are required to establish the clinical significance of these effects.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 mg kg 21 (i.v.) or 10 mg (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.

Split liver transplantation: What’s unique?

“…In rat liver, morphine preconditioning protects against IRI. This involves opioid receptors, phosphatidylinositol 3-kinase, and Akt [41] . IP protected against hepatic IRI under isoflurane anesthesia in rats.…”

The Effect of Intravenous Anesthetics on Ischemia-Reperfusion Injury

“…The mechanisms of morphine-induced hepato-protection are most likely multifactorial. These multifactorials involve opioid receptors, phosphatidylinositol-3-kinase, and Akt [11]. …”

Intrathecal morphine pretreatment ameliorated hepatic ischemia-reperfusion injury by reducing inflammation through peripheral and spinal opioid activation in rats

“…When blood reflows after a long interruption, recruited neutrophils aggressive hepatocytes directly. Numerous methods are reported to attenuate hepatic IRI including ischemic pretreatment, ischemic postconditioning and medication pretreatment [4][5][6][7]. To treat all patients in clinics and set up more efficient therapeutic methods, more clinical studies are required Neural axis analgesia is a common technique used for patients undergoing abdominal surgery [8].…”

“…Intrathecal morphine pretreatment has been showed to protect myocardial IRI [9,10]. Our previous study has demonstrated intrathecal morphine pretreatment (MPC) is necessary to have protective effects for hepatic IRI [6]. However, the related mechanisms of intrathecal MPC on hepatic IRI remain to investigate.…”