enkephalin--leucine-2-alanine and Reperfusion-Injury

enkephalin--leucine-2-alanine has been researched along with Reperfusion-Injury* in 16 studies

Other Studies

16 other study(ies) available for enkephalin--leucine-2-alanine and Reperfusion-Injury

ArticleYear
Activation of the δ opioid receptor relieves cerebral ischemic injury in rats via EGFR transactivation.
    Life sciences, 2021, May-15, Volume: 273

    Topics: Animals; Apoptosis; Brain Ischemia; Enkephalin, Leucine-2-Alanine; ErbB Receptors; Infarction, Middle Cerebral Artery; Male; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Reperfusion Injury; Transcriptional Activation

2021
Effects of D‑Ala2, D‑Leu5‑Enkephalin pre‑ and post‑conditioning in a rabbit model of spinal cord ischemia and reperfusion injury.
    Molecular medicine reports, 2019, Volume: 20, Issue:6

    It has recently been revealed that during the aorta‑clamped period, D‑Ala2, D‑Leu5‑Enkephalin (DADLE) infusion can protect the spinal cord against ischemia and reperfusion (I/R) injury. However, the protective effects of DADLE administration prior to ischemia or at the time of early reperfusion have not yet been investigated. Drug pre‑ or post‑conditioning can serve as a more valuable clinical strategy. Therefore, the present study was designed to investigate the neuroprotective effect of DADLE infusion at different time intervals in order to determine the optimum time point for ischemic spinal cord protection. A total of 40 New Zealand white rabbits were randomly divided into 5 groups: Sham‑operated (Sham), normal saline pre‑conditioning (NS), DADLE per‑conditioning (Dper), DADLE pre‑conditioning (Dpre) and DADLE post‑conditioning (Dpost). All animals were subjected to spinal cord ischemia for 30 min followed by 48 h reperfusion. Hind limb motor functions were assessed according to the Tarlov criterion when the animals regained consciousness, 6, 24 and 48 h after reperfusion. Histological analysis and the number of viable α‑motor neurons were also used to assess the extent of spinal cord injury. Compared with the NS group, the Tarlov scores and the number of normal neurons were significantly higher in the Dper group (P<0.05), which were consistent with the results of a previous study. In addition, the paraplegia rate and loss of normal motor neurons were lower in the DADLE per‑ and post‑conditioning groups compared with the DADLE pre‑conditioning; however, these were not statistically significant. DADLE 0.05 mg/kg administration at three time points all mitigated normal motor neuron injury in the anterior horn and decreased the paraplegia rates in rabbits. The therapeutic benefits appeared best in the post‑conditioning group with DADLE, and worst in the pre‑conditioning group.

    Topics: Animals; Enkephalin, Leucine-2-Alanine; Female; Ischemic Preconditioning; Male; Motor Neurons; Protective Agents; Rabbits; Reperfusion Injury; Spinal Cord; Spinal Cord Ischemia

2019
[D-Ala
    The Journal of surgical research, 2019, Volume: 241

    Meeting the metabolic demands of donor livers using normothermic ex vivo liver perfusion (NEVLP) preservation technology is challenging. The delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has been reported to decrease the metabolic demand in models of ischemia and cold preservation. We evaluated the therapeutic potential of DADLE by investigating its ability to protect against oxidative stress and hepatic injury during normothermic perfusion.. Primary rat hepatocytes were used in an in vitro model of oxidative stress to determine the minimum dose of DADLE needed to induce protection and the mechanisms associated with protection. NEVLP was then used to induce injury in rat livers and determine the effectiveness of DADLE in preventing liver injury.. In hepatocytes, DADLE was protective against oxidative stress and led to a decrease in phosphorylation of JNK and p38. Naltrindole, a δ-opioid receptor antagonist, blocked this effect. DADLE also activated the PI3K/Akt signaling pathway, and PI3K/Akt inhibition decreased the protective effects of DADLE treatment. In addition, DADLE treatment during NEVLP resulted in lower perfusate alanine aminotransferase and tissue malondialdehyde and better tissue adenosine triphosphate and glutathione. Furthermore, perfusion with DADLE compared with perfusate alone preserved tissue architecture.. DADLE confers protection against oxidative stress in hepatocytes and during NEVLP. These data suggest that the mechanism of protection involved the prevention of mitochondrial dysfunction by opioid receptor signaling and subsequent increased expression of prosurvival/antiapoptotic signaling pathways. Altogether, data suggest that opioid receptor agonism may serve as therapeutic target for improved liver protection during NEVLP.

    Topics: Allografts; Animals; Disease Models, Animal; Enkephalin, Leucine-2-Alanine; Hepatocytes; Humans; Liver; Male; Mitochondria; Organ Preservation Solutions; Oxidative Stress; Perfusion; Primary Cell Culture; Rats; Receptors, Opioid, delta; Reperfusion Injury; Tissue and Organ Harvesting

2019
DADLE improves hepatic ischemia/reperfusion injury in mice via activation of the Nrf2/HO‑1 pathway.
    Molecular medicine reports, 2017, Volume: 16, Issue:5

    Hepatic ischemia/reperfusion (I/R) injury is a common pathophysiological process that occurs following liver surgery, which is associated with oxidative stress, and can cause acute liver injury and lead to liver failure. Recently, the development of drugs for the prevention of hepatic I/R injury has garnered interest in the field of liver protection research. Previous studies have demonstrated that [D‑Ala2, D‑Leu5]‑Enkephalin (DADLE) exerts protective effects against hepatic I/R injury. To further clarify the specific mechanism underlying the effects of DADLE on hepatic I/R injury, the present study aimed to observe the effects of various doses of DADLE on hepatic I/R injury in mice. The results indicated that DADLE, at a concentration of 5 mg/kg, significantly reduced the levels of alanine aminotransferase and aspartate aminotransferase in the serum, and the levels of malondialdehyde in the liver homogenate. Conversely, the levels of glutathione, catalase and superoxide dismutase in the liver homogenate were increased. In addition, DADLE was able to promote nuclear factor, erythroid 2 like 2 (Nrf2) nuclear translocation and upregulate the expression of heme oxygenase (HO)‑1, which is a factor downstream of Nrf2, thus improving hepatic I/R injury in mice. In conclusion, the present study demonstrated that DADLE was able to significantly improve hepatic I/R injury in mice, and the specific mechanism may be associated with the Nrf2/HO‑1 signaling pathway.

    Topics: Animals; Aspartate Aminotransferases; Disease Models, Animal; Enkephalin, Leucine-2-Alanine; Heme Oxygenase-1; Liver; Liver Diseases; Male; Malondialdehyde; Membrane Proteins; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Oxidative Stress; Reperfusion Injury; Signal Transduction; Superoxide Dismutase; Up-Regulation

2017
Dose-dependent neuroprotection of delta-opioid peptide [D-Ala(2), D-Leu(5)] enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into the abdominal aorta in rabbits.
    Journal of vascular surgery, 2016, Volume: 63, Issue:4

    In our prior study, we showed that delta-opioid peptide [D-Ala(2), D-Leu(5)] enkephalin (DADLE), by regional perfusion into the abdominal aorta, could protect the spinal cord against ischemia-reperfusion (I/R) injury caused by aortic occlusion. However, the relative dose-response effects of DADLE still remain unclear. This study investigated whether DADLE has a dose-dependent efficiency on spinal cord I/R injury.. New Zealand White rabbits were randomly divided into one of six groups: normal saline (NS; n = 8), DADLE (D) groups D0.0005 (n = 8), D0.005 (n = 8), D0.05 (n = 8), and D0.5 mg/kg (n = 8), and a sham group (n = 6). In the NS and DADLE groups, spinal cord ischemia was induced by infrarenal aortic occlusion for 30 minutes. During the occlusion, the same volume of NS or DADLE at the indicated doses was infused continuously through a catheter to the distally clamped abdominal aorta. Heart rate, blood pressure, and core temperature were monitored continuously to evaluate the potential adverse effects of DADLE. Neurologic behavioral function was assessed with the Tarlov scale system at 1, 6, 24, 48, and 72 hours after reperfusion. Neuronal injury evaluation in the ventral horn of the gray matter was evaluated by counting the normal motor neurons at 72 hours after reperfusion.. The therapeutic benefits increased at the doses of DADLE from 0.0005 to 0.05 mg/kg and decreased at 0.5 mg/kg, whereas the hemodynamic parameter was suppressed temporarily at the dose of 0.5 mg/kg.. These data revealed that regional administration of DADLE through the abdominal aorta provided dose-dependent protection on spinal cord I/R in rabbits.

    Topics: Animals; Aorta, Abdominal; Catheterization, Peripheral; Disease Models, Animal; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; Female; Infusions, Intravenous; Ligation; Male; Motor Neurons; Neuroprotective Agents; Rabbits; Regional Blood Flow; Reperfusion Injury; Spinal Cord Ischemia; Time Factors

2016
Protective effect of delta opioid agonist [D-Ala2, D-Leu5] enkephalin on spinal cord ischemia reperfusion injury by regional perfusion into abdominal aorta in rabbits.
    Neuroscience letters, 2015, Jan-01, Volume: 584

    [D-Ala(2), D-Leu(5)] enkephalin (DADLE) has been reported to exhibit protective effects against hypoxic or ischemic induced brain insult. However its efficacy on the spinal cord ischemia-reperfusion injury remains unclear. Here we investigate whether DADLE could attenuate ischemia and reperfusion induced neural injury in the rabbit spinal cord. New Zealand white rabbits were subjected to spinal cord ischemia by infrarenal aortic occlusion for 30 min. In the period of spinal cord ischemia, DADLE 0.5 mg/kg or NS were infused continuously into the distal clamped abdominal aorta. The heart rate, blood pressure, and core temperature were monitored continuously during the whole experimental procedure. Then the neurological behavioral function was assessed with Tarlov scale system at 1h, 6h, 24h, 48 h after reperfusion, and neuronal injury evaluation in the ventral horn of gray matter was measured by counting the normal motor neurons at 48 h after reperfusion. Comparing with the control group, the Tarlov scores were significantly higher and the incidences of paraplegia were significantly lower in the DADLE group at four time-point recorded. In addition, the normal neurons numbers in the DADLE group were significant more than those in the control group at 48 h after reperfusion. These results suggested that DADLE infused into the abdominal aorta during ischemia period could attenuate behavioral retardation and the loss of normal motor neuron induced by ischemia-reperfusion in rabbits.

    Topics: Animals; Aorta, Abdominal; Enkephalin, Leucine-2-Alanine; Female; Hemodynamics; Male; Neurons; Neuroprotective Agents; Perfusion; Rabbits; Receptors, Opioid, delta; Reperfusion Injury; Spinal Cord Ischemia

2015
Protection of rat intestinal epithelial cells from ischemia/reperfusion injury by (D-Ala2, D-Leu5)-enkephalin through inhibition of the MKK7-JNK signaling pathway.
    Molecular medicine reports, 2015, Volume: 12, Issue:3

    Previous studies have demonstrated that (D‑Ala2, D‑Leu5)‑enkephalin (DADLE) protects rats from hepatic ischemia/reperfusion (I/R) injury. In the present study, DADLE was also observed to alleviate IR‑induced intestinal epithelial cell injury in rats by inhibiting mitogen‑activated protein kinase kinase 7 (MKK7)‑c‑Jun N‑terminal kinase (JNK) pathway signaling. To investigate the protective effect of DADLE on hypoxia/reoxygenation injury in rat intestinal epithelial cells, rat intestinal epithelial cells were treated with different concentrations of DADLE, following which the cell survival rate was determined using a tetrazolium (MTT) colorimetric assay, and apoptosis was determined using flow cytometry. To confirm whether the protective effect of DADLE was due to its effect on MKK7‑JNK signaling, the phosphorylation levels of MKK7 and JNK were analyzed using western blot analysis following treatment with different concentrations of DADLE. The results demonstrated that, following treatment with DADLE, the survival rate of the rat intestinal cells subjected to I/R‑induced injury increased significantly and the apoptotic rate decreased in a concentration‑dependent manner. In addition, the levels of phosphorylated MKK7 and JNK decreased in a concentration‑dependent manner following treatment with DADLE. Silencing the gene expression of MKK7 using small interfering RNA prior to DADLE treatment resulted in a reduction in the protective effects of DADLE on the rat intestinal epithelial cells subjected to I/R injury. Collectively, the results of the present study demonstrated that the protective effects of DADLE in I/R injury in rat intestinal cells occurred through inhibition of the MKK7‑JNK pathway.

    Topics: Animals; Apoptosis Regulatory Proteins; Cell Line; Cell Proliferation; Cell Survival; Disease Models, Animal; Enkephalin, Leucine-2-Alanine; Epithelial Cells; Female; G1 Phase Cell Cycle Checkpoints; Intestines; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Kinase 7; MAP Kinase Signaling System; Neuroprotective Agents; Phosphorylation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA Interference; RNA, Small Interfering

2015
[D-Ala2,D-Leu5]-enkephalin (DADLE) and morphine-induced postconditioning by inhibition of mitochondrial permeability transition pore, in human myocardium.
    Experimental biology and medicine (Maywood, N.J.), 2013, Volume: 238, Issue:4

    The aim of the study was to examine the cardioprotective effect of morphine and Delta 2 opioid D-Ala2-Leu5 enkephalin(DADLE) administered, at early reoxygenation, in isolated human myocardium exposed to hypoxia–reoxygenation. Then,we tested the involvement of mitochondrial permeability transition pore in morphine and DADLE-induced postconditioning.Human right atrial trabeculae were obtained during cardiac surgery (coronary artery bypass and aortic valve replacement).Isometrically contracting isolated human right atrial trabeculae were exposed to 30-min hypoxia and 60-min reoxygenation(control group). In treatment groups, morphine 0.5 mmol, DADLE 10 nmol, DADLE 50 nmol and DADLE 100 nmol were administered during the first 15 min of reoxygenation. In two additional groups, morphine and DADLE 100 nmol were administered in the presence of atractyloside 50 mmol, the mitochondrial permeability transition pore opener. The force of contraction at the end of 60-min reoxygenation period (FoC60 expressed as % of baseline) was compared (mean+standard deviation) between the groups by an analysis of variance. Morphine (FoC60: 81+9% of baseline), DADLE50 nmol (FoC60: 76+11% of baseline) and DADLE 100 nmol (FoC60: 81+4% of baseline) increased significantly (P,0.001) the FoC60 as compared with the control group (FoC60: 53+3% of baseline). DADLE 10 nmol did not modify the FoC60 (50+9% of baseline; P ¼ 0.60 versus control group). The enhanced recovery of FoC60 induced by morphine and DADLE 100 nmol were abolished in the presence of atractyloside (FoC60: respectively 57+6% and 44+7% of baseline;P, 0.001). In conclusion, the administration of morphine and DADLE, in early reoxygenation period, protected human myocardium, in vitro, against hypoxia–reoxygenation injury, at least in part, by the inhibition of mitochondrial permeability transition pore opening.

    Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Atractyloside; Coronary Vessels; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; Enzyme Inhibitors; Heart; Humans; In Vitro Techniques; Ischemic Postconditioning; Middle Aged; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Morphine; Reperfusion Injury

2013
Protective effects of the delta opioid peptide [D-Ala2, D-Leu5]enkephalin in an ex vivo model of ischemia/reperfusion in brain slices.
    CNS neuroscience & therapeutics, 2012, Volume: 18, Issue:9

    The delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) plays a key role in neuronal protection against both hypoxic and ischemic conditions. However, the cellular mechanisms of action of DADLE under these conditions remain unclear.. Ischemia was simulated with perfusing the brain slices with glucose-free artificial cerebrospinal fluid. Apoptosis was examined using an in situ cell death detection kit and expressed as the percentage of positively labeled neurons relative to total number of neurons. PCR was performed by adding cDNA, 5 pm dNTP, 1 μL Taqase, and primers. PCR products were separated with electrophoresis, stained with ethidium bromide, and visualized under ultraviolet light.. To investigate the potential effects of DADLE in an ex vivo model of cerebral ischemia/reperfusion.. DADLE attenuated lactic dehydrogenase release and neuronal apoptosis in a concentration-dependent manner. The protective effects of DADLE were attenuated by representative selective delta2, but not delta1 opioid antagonists. Treatment with PD98059, a selective inhibitor of ERK kinase (MEK), also blocked the protective effect of DADLE as well as ERK phosphorylation induced by DADLE.. Endogenous opioid peptides could promote cell survival via delta2 opioid receptors, possibly through the downstream MEK-ERK pathway.

    Topics: Animals; Apoptosis; Brain Ischemia; Cerebral Cortex; Disease Models, Animal; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; In Vitro Techniques; L-Lactate Dehydrogenase; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Reperfusion Injury

2012
delta-Opioid receptor activation attenuates oxidative injury in the ischemic rat brain.
    BMC biology, 2009, Aug-26, Volume: 7

    We have recently shown that delta-opioid receptors (DORs) play an important role in neuroprotection from hypoxic injury via the regulation of extracellular signaling-regulated kinase (ERK) and cytochrome c release. Since ERK and cytochrome c are differentially involved in caspase signaling of oxidative injury that significantly contributes to neuronal damage in ischemia/reperfusion, we considered if DOR activation protects the ischemic brain by attenuating oxidative injury.. We observed that, in a model of cerebral ischemia with middle cerebral artery occlusion, DOR activation increased the activity of major antioxidant enzymes, glutathione peroxidase and superoxide dismutase, and decreased malondialdehyde and nitric oxide levels in the cortex exposed to cerebral ischemia/reperfusion. In addition, DOR activation reduced caspase 3 expression, though it did not significantly affect the increase in interleukin (IL)1beta and tumor necrosis factor (TNF)alpha expression at the same timepoint. PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) extracellular signaling-regulated kinase kinase, accelerated animal death during ischemia/reperfusion.. DOR activation attenuates oxidative injury in the brain exposed to ischemia/reperfusion by enhancing antioxidant ability and inhibiting caspase activity, which provides novel insights into the mechanism of DOR neuroprotection.

    Topics: Animals; Brain Ischemia; Caspase 3; Enkephalin, Leucine-2-Alanine; Gene Expression Regulation; Glutathione Peroxidase; Hippocampus; Interleukin-1beta; Male; Malondialdehyde; Models, Biological; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Reperfusion Injury; RNA, Messenger; Superoxide Dismutase; Tumor Necrosis Factor-alpha

2009
Delta-opioid receptor ligands in shock treatment.
    Resuscitation, 2009, Volume: 80, Issue:11

    Topics: Animals; Disease Models, Animal; Enkephalin, Leucine-2-Alanine; Reperfusion Injury; Shock, Hemorrhagic; Treatment Outcome

2009
The delta-opioid receptor agonist DADLE at reperfusion protects the heart through activation of pro-survival kinases via EGF receptor transactivation.
    American journal of physiology. Heart and circulatory physiology, 2007, Volume: 293, Issue:3

    The specific delta-opioid receptor agonist [D-Ala(2)-D-Leu(5)]enkephalin (DADLE) protects against infarction in the heart when given before ischemia. In rabbit, this protection leads to phosphorylation of the pro-survival kinases Akt and extracellular signal-regulated kinase (ERK) and is dependent on transactivation of the epidermal growth factor receptor (EGFR). DADLE reportedly protects rat hearts at reperfusion. We therefore tested whether DADLE at reperfusion could protect isolated rabbit hearts subjected to 30 min of regional ischemia and 120 min of reperfusion and whether this protection is dependent on Akt, ERK, and EGFR. DADLE (40 nM) was infused for 1 h starting 5 min before reperfusion and reduced infarct size from 31.0 +/- 2.3% in the control group to 14.6 +/- 1.6% (P = 0.01). This protection was abolished by cotreatment of the metalloproteinase inhibitor (MPI) and the EGFR inhibitor AG1478. In contrast, 20 nM DADLE, although known to be protective before ischemia, failed to protect. Western blotting revealed that DADLE's protection was correlated to increase in phosphorylation of the kinases Akt and ERK1 and -2 in reperfused hearts (2.5 +/- 0.5, 1.6 +/- 0.2, and 2.3 +/- 0.7-fold of baseline levels, P < 0.05 vs. control). The DADLE-dependent increases in Akt and ERK1/2 phosphorylation were abolished by either MPI or AG1478, confirming a signaling through the EGFR pathway. Additionally, DADLE treatment increased phosphorylation of EGFR (1.4 +/- 0.2-fold, P = 0.03 vs. control). Thus the delta-opioid agonist DADLE protects rabbit hearts at reperfusion through activation of the pro-survival kinases Akt and ERK and is dependent on the transactivation of the EGFR.

    Topics: Animals; Enkephalin, Leucine-2-Alanine; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocardial Infarction; Oncogene Protein v-akt; Rabbits; Receptors, Opioid, delta; Reperfusion Injury; Transcriptional Activation

2007
Effect of opiate peptide dalargin and des-Tyr-dalargin on cardiac pump function during ischemia-reperfusion.
    Bulletin of experimental biology and medicine, 2004, Volume: 137, Issue:1

    Experiments on isolated perfused rat heart showed that nonselective micro- and delta-opiate receptor agonist dalargin decreased contractility of the intact heart, but had no effect on pump function of the ischemic myocardium. Dalargin analogue des-Tyr-dalargin not binding to opiate receptors decreased contractility of intact myocardium and isolated heart exposed to 45-min total ischemia. We hypothesize that the influence of dalargin is related to activation of cardiac delta-opiate receptors, while the inotropic effect of des-Tyr-dalargin is mediated by other receptors.

    Topics: Animals; Enkephalin, Leucine-2-Alanine; Heart; In Vitro Techniques; Myocardial Contraction; Rats; Reperfusion Injury; Ventricular Pressure

2004
[D-Ala2, D-Leu5] enkephalin (DADLE) protects liver against ischemia-reperfusion injury in the rat.
    The Journal of surgical research, 2003, Volume: 114, Issue:1

    [D-Ala(2), D-Leu(5)] enkephalin (DADLE) is a synthetic delta class of opioid and is reported to induce hibernation as well as hibernation induction trigger (HIT) in the serum of hibernating mammals. DADLE and HIT have been demonstrated to protect the heart, lung, and jejunum against ischemia-reperfusion (I-R) injury. In the present study, we examined the effect of DADLE on I-R injury of the liver in rats.. After administration of DADLE (DADLE group) or normal saline as a vehicle (Control group), partial hepatic ischemia was induced by occluding the vessels supplying 92% of the liver for 45 min, followed by declamping the vessels and resection of the non-ischemic lobe. After 120 min of reperfusion, serum glutamic-pyruvic transaminase (GPT), hyaluronic acid (HA) levels, and concentrations of malondialdehyde (MDA) of the liver tissue were measured. Additionally, bile output from the ischemic lobes was measured after reperfusion.. GPT levels were significantly lower in the DADLE group as compared to those of the Control group (P < 0.05), but the serum levels of HA were not different between the two groups. The concentrations of MDA of the liver tissue were significantly lower in the DADLE group than in the Control group (P < 0.01). The bile output after reperfusion was not significantly different between the two groups.. DADLE protects against I-R injury in hepatocytes, but not in the sinusoidal endothelial cells of the liver in rats. An anti-oxidative effect is suggested to be responsible for this effect.

    Topics: Alanine Transaminase; Analgesics, Opioid; Animals; Bile; Cytoprotection; Enkephalin, Leucine-2-Alanine; Hibernation; Hyaluronic Acid; Liver; Liver Diseases; Male; Malondialdehyde; Rats; Rats, Wistar; Reperfusion Injury

2003
Delta opiates increase ischemic tolerance in isolated rabbit jejunum.
    Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2002, Volume: 9, Issue:6

    Mammalian hibernation is mediated by humoral agonists of the delta opioid receptor (DOR). Moreover, transfer of either humoral or synthetic DOR agonists to non-hibernators reportedly induces a state of improved myocardial ischemic tolerance.. To determine whether the DOR agonist D-Ala 2, D-Leu 5, enkephalin (DADLE) similarly elicits protection in noncardiac-i.e., mesenteric-tissue.. In Protocols 1 and 2, the authors developed and characterized an in vitro model of mesenteric ischemia/reperfusion in isolated rabbit jejunum by documenting the effect of increasing ischemic duration (0 to 120 minutes) and the relative importance of glucose and/or oxygen deprivation on the evolution of jejunal injury. In Protocol 3, jejunal segments were randomized to receive either no treatment (controls) or 15 minutes of pretreatment with 1 microM DADLE, followed by 60 minutes of simulated ischemia and 30 minutes of reperfusion. Jejunal injury was quantified by repeated, time-matched assessment of peak contractile force evoked by 1 microM acetylcholine (all protocols) and delineation of tissue necrosis (Protocol 1).. Development of significant jejunal injury required combined oxygen/glucose deprivation. Moreover, there was a direct relationship between ischemic duration and tissue injury, and a significant inverse correlation between reperfusion contractile force (% of baseline) and the extent of smooth muscle necrosis (r(2) = 0.87; p < 0.01). Most notably, mesenteric ischemia/reperfusion injury was attenuated by DADLE: reperfusion contractile force was 47 +/- 5% versus 36 +/- 5% in DADLE-treated versus control segments (p < 0.01).. Treatment with the delta opioid agonist DADLE increases ischemic tolerance of isolated rabbit jejunum.

    Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; Glucose; Hypoxia; In Vitro Techniques; Ischemia; Jejunum; Muscle Contraction; Muscle, Smooth; Rabbits; Receptors, Opioid, delta; Reperfusion Injury; Splanchnic Circulation

2002
delta Opioid extends hypothermic preservation time of the lung.
    The Journal of thoracic and cardiovascular surgery, 1996, Volume: 111, Issue:1

    To test the hypothesis that a delta opioid, DADLE ([D-Ala2, D-Leu5]-enkephalin), could protect tissue from ischemic damage during hypothermic lung preservation, we studied three groups of rats. In group 1 (n = 8), lung function was studied immediately after harvesting. In group 2 (n = 8), the lung was flushed with 4 degrees C Euro-Collins solution and preserved for 24 hours. In group 3 (n = 8), the lung was flushed with 4 degrees C Euro-Collins solution plus DADLE (1 mg/kg) and preserved for 24 hours. Lung function was studied by using a living rat perfusion model. Venous blood from the host rat perfused the pulmonary artery of the isolated lung. Blood from the isolated lung was returned to the carotid artery of the host rat with a roller pump. Severe pulmonary edema, hemorrhage, and occlusive pulmonary artery resistance occurred in group 2 within 30 minutes of perfusion. Perfusion studies were carried out for more than 60 minutes in groups 1 and 3. Pulmonary blood flow was lower in group 2 than in either group 1 or group 3. Pulmonary vascular resistance was much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway pressure and airway resistance were much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway resistance was also higher in group 3 than in group 1 after 20 minutes of perfusion (p < 0.05). Oxygen tensions from the pulmonary vein of the isolated lung in group 2 were lower than those in groups 1 and 3 (p < 0.05). Alveolar-arterial oxygen difference was much higher in group 2 than in groups 1 and 3 (p < 0.05). Lung tissue wet/dry weight ratio after perfusion was much higher in group 2 than in groups 1 and 3. The results clearly show, for the first time, that DADLE can effectively enhance hypothermic lung preservation in rats.

    Topics: Airway Resistance; Animals; Enkephalin, Leucine-2-Alanine; Hypertonic Solutions; Lung; Lung Transplantation; Organ Preservation; Pulmonary Circulation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors

1996