Opioid receptor-independent protection of ischemic rat hepatocytes by morphine

Kim, Jae-Sung; Lemasters, John J.

doi:10.1016/j.bbrc.2006.10.153

Cited by 13 publications

(6 citation statements)

References 33 publications

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“…21 A previous study using a hepatocyte anoxia/reoxygenation injury in vitro demonstrated that morphine's cytoprotective effects are independent of opioid receptor activation. 22 Nonparenchymal cells such as Kupffer cells or stellate cells are known to express opioid receptors any could also be the target cells of morphine preconditioning. Their role in in vivo hepato-protection might not be reflected in cell line studies involving only hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Wong

Man

et al. 2012

British Journal of Anaesthesia

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† 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.

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Section: Discussionmentioning

confidence: 99%

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

Wang

Wong

Man

et al. 2012

British Journal of Anaesthesia

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“…Kim and Lemasters [106] noted that in cultured rat hepatocytes, morphine improved cell viability after anoxia/reperfusion and increased NO generation, which was attenuated by ATP-sensitive K + channel blockers; however, treatment with opioid receptor antagonists did not reverse the cytoprotection conferred by morphine, indicating that morphine prevents anoxia/ reperfusion injury to hepatocytes and that the protective mechanisms may be associated with K + channels and NO, but are independent of opioid-mediated signaling.…”

Section: Digestive Systemmentioning

confidence: 94%

Interactions between morphine and nitric oxide in various organs

Toda¹,

Kishioka

Hatano

et al. 2009

J Anesth

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Nitric oxide (NO) plays obligatory roles as an important intercellular messenger in the control of physiological functions and it also participates in pathophysiological interventions. This labile, gaseous molecule is also involved in mechanisms underlying the beneficial and untoward actions of therapeutic agents. Endogenous NO is formed by endothelial and neurogenic NO synthases that are constitutively present mainly in the endothelium and nervous system, respectively, and is induced by lipopolysaccharides or cytokines mainly in mitochondria, glial cells, and vascular smooth muscle cells. NO modulates the effects of morphine on processes involving the central nervous system, such as learning, memory, convulsion, thermoregulation, and penile erection. This molecule is also involved in the modification of morphine actions on the cardiovascular, digestive, and respiratory systems. Morphine regulates NO bioavailability in various organs. NO formed by inducible NO synthase participates in some morphine actions in the immune system. Information concerning interactions between NO and morphine and other opioids in a variety of organs and tissues is quite useful in establishing new strategies for minimizing the noxious and unintended reactions that are frequently encountered during analgesic therapy.

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“…Opioid preconditioning with Tan-67 induces opioid receptor-dependent neuroprotection against ischemia in rats (1319). Opioid receptor-independent protection of ischemic rat hepatocytes was observed following morphine (581). Central and peripheral opioid receptor antagonists block the cardioprotective effects of fentanyl (649).…”

Section: B Cardioprotection and Ischemic Preconditioningmentioning

confidence: 99%

Endogenous opiates and behavior: 2006

Bodnar

2007

Peptides

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This paper is the 29th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning 30 years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).

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Opioid receptor-independent protection of ischemic rat hepatocytes by morphine

Cited by 13 publications

References 33 publications

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

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

Interactions between morphine and nitric oxide in various organs

Endogenous opiates and behavior: 2006

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