Preconditioning with L-alanyl-L-glutamine in a Mongolian Gerbil model of acute cerebral ischemia/reperfusion injury

Pires, Vilma Leite de Sousa; Souza, José Reniclebson Feitosa de; Guimarães, Sérgio Botelho; Filho, Antônio Ribeiro da Silva; Garcia, José Huygens Parente; Vasconcelos, Paulo Roberto Leitão de

doi:10.1590/s0102-86502011000700004

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…Cerebral ischemia is a leading cause of death and disability worldwide and diabetes is a risk factor for ischemic cerebrovascular diseases [5]. Reperfusion following cerebral ischemia leads to the generation of pro-oxidant species which cause neuronal damage by acting directly on macromolecules, including proteins, lipids and DNA, or indirectly by interfering with cell signaling pathways and gene expression regulation [6]. Furthermore, several mechanisms are responsible for diabetic neuropathy including dyslipidemia, inflammation and apoptosis [4, 7, 8] .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effect of resveratrol in diabetic cerebral ischemic-reperfused rats through regulation of inflammatory and apoptotic events

Mohamed

Elswefy

Hasan

et al. 2014

Diabetol Metab Syndr

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BackgroundDiabetes and cerebral ischemic-reperfusion are among the most common causes of neurological complications in Egypt. The prevalence of diabetes in Egypt is high and it can be considered as a major clinical and public health problem.MethodsBlood glucose, lipid profile, oxidative stress makers (cerebral MDA & GSH), cerebral interleukin-4 (IL-4) level and cerebral cyclooxygenase-2 (COX-2) gene expression were measured in male albino rats weighing 200 ± 20 g. The rats were divided into five groups, normal control group, diabetic group (diabetes was induced by single dose of streptozotocin [STZ]), diabetic cerebral ischemic-reperfused group, two treated groups (diabetic and diabetic ischemic-reperfused), both groups treated with resveratrol. Histological study was done using H&E, AgNOR and cresyl violet stains. Immunohistochemistry for Bax and COX-2 was done with morphometric study.ResultsDiabetic and diabetic cerebral ischemic- reperfused rats showed significant increase in serum glucose level, serum TAG, serum LDL-C, atherogenic index, cerebral MDA and upregulation of COX-2 gene expression. These groups showed significant decrease in serum HDL, cerebral IL-4 and depletion of cerebral GSH when compared to normal control rats. Treating these groups with resveratrol resulted in significant decrease in serum glucose level, serum TAG, TC, serum LDL-C, atherogenic index, cerebral MDA and downregulation of COX-2 gene expression. The results of COX-2 gene expression were confirmed by COX-2 immunohistochemistry. Also, significant increase in serum HDL, cerebral IL-4 and cerebral GSH contents could be observed in these treated groups as compared to normal control group. Cerebral apoptotic index and optical density of Bax reaction revealed significant increase in diabetic and diabetic cerebral ischemic-reperfused rats while treatment of these groups with resveratrol resulted in significant decrease in cerebral apoptotic index and optical density of Bax reaction. These apoptotic results were confirmed with AgNOR and cresyl violet stains.ConclusionThe results of this research suggest that upregulation of cerebral COX-2 gene along with the decrease in cerebral IL-4 and enhanced cerebral apoptosis is critically involved in cerebral damage associated with diabetes and cerebral ischemic-reperfusion. Resveratrol can ameliorate these effects and has promising neuroprotective effect in diabetic-induced cerebral complications.

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Section: Introductionmentioning

confidence: 99%

Neuroprotective effect of resveratrol in diabetic cerebral ischemic-reperfused rats through regulation of inflammatory and apoptotic events

Mohamed

Elswefy

Hasan

et al. 2014

Diabetol Metab Syndr

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“…Previous intravenous infusion of L-Ala-Gln in gerbils subjected to brain IR has been shown to decrease degeneration of the nucleus (pyknosis) and cell death (red neurons) in the cerebral tissue 6 . Preconditioning with mixtures of oils containing high ratio ω-6/ω-3 and low ω-9/ω-6 relationship protected brain neurons against I/R injury in an experimental model of global cerebral ischemia/reperfusion by decreasing red neurons count in hippocampus area CA3 1 .…”

Section: Red Neuron Countingmentioning

confidence: 99%

“…Previous infusion of L-Ala-Gln has been shown to reduce oxidative stress and brain cell nuclear degeneration in gerbils subjected to brain ischemia/reperfusion (I/R) injury 6 .…”

Section: Introductionmentioning

confidence: 99%

Preconditioning with L-alanyl-glutamine upon cerebral edema and hypocampus red neurons counting in rats subjected to brain ischemia /reperfusion injury

Vasconcelos

Guimarães²,

Campelo³

et al. 2015

Acta Cir. Bras.

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Conception, design, intellectual and scientific content of the study, critical revision, final approval. ABSTRACT PURPOSE:To evaluate the effects of the dipeptide L-alanyl-glutamine (L-Ala-Gln) as a preconditioning agent to potentially promote reduction in the intensity of lesion or induction of resilience in rats subjected to global cerebral ischemia/reperfusion (I/R) injury. METHODS:Thirty-six male Wistar rats weighing 280-300g were randomly assigned to six groups (n=6). Groups Sham 1h and 24hwere treated with saline and spared of further interventions. The remaining groups were submitted to clamping of the common carotid arteries for 30 minutes (ischemia) and treated with saline (SS) or L-Ala-Gln. Brain reperfusion was allowed for 1or 24 h. L-Ala-Gln was administered intravenously (0.75g/kg) 30 minutes before sham procedure or induction of global brain I/R injury. Brain edema and red neuron counting were determined. Results were expressed as Mean±SD for normal results and Median±Percentile for non parametric data. Significance was established at p<0.05. RESULTS:Global I/R injury promoted an increase in brain edema at 24 h after reperfusion, whereas preconditioning with L-Ala-Gln induced no change in edema. On the other hand, L-Ala-Gln preconditioning decreased significantly red neurons counting both at 1h and 24h post reperfusion (p<0.05). CONCLUSION:There was a significant preconditioning effect with L-Ala-Gln decreasing cell death (red neurons counting) at early (1h) and late reperfusion (24h) in the cerebral tissue.

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“…NLAG can directly scavenge, significantly improve the anti-apoptotic ability, and reduce the release of inflammatory factors, chemokines and adhesion molecules ( 5 , 6 ). In addition, NLAG has a protective effect on the kidney and liver against IRI ( 7 , 8 ). However, any protective effects and the underlying mechanism of NLAG on the myocardial IRI remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion

et al. 2018

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To explore the protective effect of N(2)-L-alanyl-L-glutamine (NLAG) on myocardial ischemia-reperfusion injury (IRI), and observe the influence of NLAG on the Janus activated kinase signal transducer 2 and activator of transcription 3 (JAK2/STAT3) signaling pathway-associated molecules. Wistar rats were randomly divided into three groups: Sham, IRI and NLAG. In the IRI rat model, the cardiac hemodynamics, the maximum rate of left ventricular pressure (+dP/dtmax) and the left ventricular end-diastolic pressure (LVDP) were recorded. Hematoxylin-eosin and Masson staining were used to detect myocardial histological changes. The levels of plasma interleukin (IL)-1β and −6, tumor necrosis factor (TNF)-α, lactase dehydrogenase (LDH), troponin (cTn)I, creatine kinase (CK), heart type fatty acid binding protein (hFABP), malondialdehyde (MDA) and succinate dehydrogenase (SDH) were determined with ELISA. The protein expression levels of B-cell lymphoma (Bcl)-2, Bcl2-associated X protein (Bax), Caspase-3, JAK2, phosphorylated (p)-JAK2, STAT3 and p-STAT3 were detected by western blot analysis. The IRI model demonstrated notable myocardial injury; myocardial cells were arranged disorderly with some nuclei disappearing, and cardiac muscular fibers were degenerated. Following 60 min of reperfusion, LVDP, HR and +dP/dtmax were 31.3±4.53 mmHg, 239.17±8.45 beats/min and 615.17 mmHg/sec, respectively. Compared with the Sham group, the levels of LDH, cTnI, CK, hFABP release, inflammatory factors (IL-1β, IL-6 and TNF-α) and oxygen free radical (MDA and SDH) levels were increased in the IRI group. In the NLAG group, myocardial injury was improved, the concentrations of LDH, cTnI, CK, hFABP, IL-1β, IL-6, TNF-α, MDA were decreased, and SDH release was increased compared with the IRI group. In addition, NLAG significantly increased Bcl-2, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression, and decreased Bax protein expression compared with the IRI group. In conclusion, myocardial ischemia-reperfusion can lead to myocardial cell apoptosis and myocardial injury and NLAG attenuates the IRI-induced mitochondrial oxidative stress injury and apoptosis by activating the JAK2/STAT3 signaling pathway, thus exerting protective effects against IRI.

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Preconditioning with L-alanyl-L-glutamine in a Mongolian Gerbil model of acute cerebral ischemia/reperfusion injury

Cited by 11 publications

References 27 publications

Neuroprotective effect of resveratrol in diabetic cerebral ischemic-reperfused rats through regulation of inflammatory and apoptotic events

Neuroprotective effect of resveratrol in diabetic cerebral ischemic-reperfused rats through regulation of inflammatory and apoptotic events

Preconditioning with L-alanyl-glutamine upon cerebral edema and hypocampus red neurons counting in rats subjected to brain ischemia /reperfusion injury

Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion

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