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Effects of G administration on necrosis markers in ex vivo and in vivo models of myocardial I/R injury. (A) LDH release in myocardial effluent from isolated perfused rat heart. Control-postischemic infusion of KHB; G-postischemic infusion of KHB with 225 μM G. Values are the means ± SEM of 8 experiments and are expressed in IU/g dry wt. for 5-min Langendorff perfusion before or after global ischemia (early reperfusion). * p<0.05 vs. the value before ischemia; # p<0.05 vs. the value in control. Activities of LDH (B) and CK-MB (C) in blood plasma in rats in vivo. St. state-steady state; Control-i.v. administration of saline at the onset of reperfusion; G-i.v. administration of peptide G (1.4 μmol/kg) at the onset of reperfusion. Values are the means ± SEM for 8 experiments. * P<0.05 vs. steady state; # P<0.05 vs. control.
Source publication
Background and purpose
Galanin is an endogenous peptide involved in diverse physiological functions in the central nervous system including central cardiovascular regulation. The present study was designed to evaluate the potential effects of the short N-terminal galanin fragment 2-15 (G) on cardiac ischemia/reperfusion (I/R) injury.
Experimental...
Contexts in source publication
Context 1
... effects were combined with a significant increase in PCr recovery, better preservation of ΣCr and a substantial reduction in myocardial lactate content. LDH leakage in the perfusate before ischemia did not differ significantly between the studied groups ( Figure 6A). In control, the release of LDH at early reperfusion increased by more than two- fold compared with the value before ischemia. ...
Context 2
... infusion significantly decreased LDH leakage compared with control, thus suggesting fewer defects of the sarcolemma. In vivo studies on activity of necrosis marker showed that plasma level of CK-MB and LDH increased by 8 and 20 times respectively, at the end of reperfusion in the control animals ( Figure 6B, 6C). Administration of G at dose of 0.35 or 2.10 μmol/kg did not significantly reduce the activity of both enzymes compared with control. ...
Context 3
... treatment with G at dose of 0.7 or 1.4 μmol/kg reduced the CK-MB and LDH activity (on average 1.6 and 1.5-times respectively, compared to the values in the control group). Decrease in the plasma activity of both necrosis markers in the group G-1.4 is shown in Figure 6B, 6C. These experiments demonstrated a direct cardioprotective action of exogenous peptide G on the heart after ischemia and reperfusion. ...
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Citations
... We speculate that PNX cardioprotective activity might take place solely during the acute phase of in� jury, as was the case of a different neuropeptide: galanin. [37][38][39] On balance, further studies of plasma PNX concentration in acute heart damage, such as acute myocardial infarction, are necessary. Moreover, we have found correlation between PNX level and LDL cholesterol and triglycerides concen� tration in H� patients and controls, respectively. ...
Introduction
Heart failure (HF) nowadays in western countries is an immense problem largely due to its social impact as well as an economic burden. A widely accepted biomarker-based strategy to establish prognosis and predict re-hospitalization events in HF is lacking. Currently, besides natriuretic peptides and cardiac troponins, a variety of molecules are being studied. Phoenixin (PNX) is a neuropeptide mainly involved in the regulation of gonadotropin secretion. Recently, a significant cardioprotective effect of PNX was reported.
Aim
The aim of this study was to measure PNX plasma concentration in a group of HF with reduced ejection fraction (HFrEF) patients and to compare it to levels found in HF-negative participants.
Material and methods
A group of 74 HFrEF patients and a control group consisting of 40 participants without systolic or diastolic myocardial dysfunction were studied. Each individual underwent anthropometric measurements, laboratory testing, clinical and echocardiographic examination. To evaluate PNX plasma concentration, an immunoenzymatic assay (ELISA) was performed.
Results and discussion
PNX plasma concentration in the HFrEF group was not statistically different than in the control group. No significant correlation between PNX level and age, sex, BMI, HF etiology, diabetes or atrial fibrillation presence was found. PNX concentration correlated positively with total and LDL cholesterol blood levels in HFrEF patients. A negative correlation was found with creatinine in HFrEF, uric acid and triglycerides levels as well as AlAT activity in the control group.
Conclusions
There is no significant difference in PNX plasma concentration between HF and non-HF individuals. PNX role in cardiovascular disease requires further investigation.
... 2-15) (WTLNSAGYLL-NH 2 и WTLNSAGYLLGPHA-ОН соответственно), связываясь с рецептором GalR2, оказывают защитное действие на кардиомиоциты при И/Р повреждении. Оно обусловлено снижением образования супероксидных радикалов в митохондриях и уменьшением гибели клеток от апоптоза и некроза [3,4]. Впоследствии был синтезирован ряд пептидных аналогов фрагментов галанина (а.о. ...
... 2-11) и (а.о. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] с сохранением фармакофорных а.о., ответственных за связывание с рецептором GalR2, которые также обладали кардиотропными свойствами [5]. Наиболее эффективной оказалась химерная молекула, представляющая последовательность галанина (а.о. ...
... Наиболее эффективной оказалась химерная молекула, представляющая последовательность галанина (а.о. [2][3][4][5][6][7][8][9][10][11][12][13], дополненную природным дипептидом карнозином WTLNSAGYLLGPβAH-OH (Гал) [6]. Гал улучшал параметры функции сердца крыс, интегрированность клеточных мембран и энергетическое состояние кардиомиоцитов, а также снижал образование АФК, продуктов перекисного окисления липидов (ПОЛ) и увеличивал активность антиоксидантных ферментов в сердце при моделировании окислительного стресса in vitro и in vivo [7]. ...
Antioxidant and anti-ischemic properties of the pharmacological agonist of galanin receptor GalR2 WTLNSAGYLLGPβAH (Gal) and its C-terminal fragment, dipeptide carnosine (βAH), were studied in the model of regional ischemia and reperfusion of the rat heart in vivo in the dose range of 0.5-5.0 mg/kg and Cu²⁺-induced free radical oxidation of low density lipoproteins (LDL) of human plasma in vitro for peptide concentrations of 0.01 mM and 0.1 mM. Gal was obtained by automatic solid phase synthesis using the Fmoc methodology; its structure was characterized by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Intravenous administration of the optimal dose of Gal (1 mg/kg) to rats after ischemia was more effective than carnosine in reducing of the myocardial infarct size and the activity of creatine kinase-MB and lactate dehydrogenase in blood plasma at the end of reperfusion. It also improved the metabolic state of the reperfused myocardium and reduced the formation of peroxidation products during reperfusion. Gal reduced more effectively the formation of adducts of hydroxyl radicals in the interstitium of the area at risk (AAR) of the rat heart than carnosine. Carnosine at a dose of 1 mg/kg more effectively increased the activity of catalase and glutathione peroxidase in the AAR by the end of reperfusion compared to Gal. In a model of Cu²⁺-initiated oxidation of human plasma LDL 0.1 mM carnosine demonstrated a significantly more pronounced reduction in the formation of lipid radicals compared to Gal. The results show that Gal can be considered as a promising agent that reduces myocardial injury during reperfusion and oxidative stress.
... We have previously shown that exogenous neuropeptide galanin (G) and its N-terminal fragments attenuate cardiac damage in doxorubicin-induced cardiomyopathy and ischemia/reperfusion stress. In particular, N-terminal fragments of galanin (2-11) WTLNSAGYLL-NH2 and (2-15) WTLNSAGYLLGPHA-OH increased cell viability, inhibited apoptosis and the formation of superoxide radical anion and hydrogen peroxide in mitochondria of rat cardiomyoblast H9c2 cells during hypoxia-reoxygenation Pisarenko et al. 2017). Intravenous administration of these peptides to rats after regional myocardial ischemia decreased infarct size and activities of the necrosis markers in blood plasma at the end of reperfusion (Serebryakova et al. 2019). ...
... In recent years, the antioxidant properties of G and its N-terminal fragments have been observed in various in vitro and in vivo experimental models. G fragments (2-11) WTLNSAGYLL-NH2 and (2-15) WTLNSAGYLLGPHA-OH inhibited apoptosis and excessive formation of mitochondrial ROS in response to oxidative stress in rat cardiomyoblast H9c2 cells Pisarenko et al. 2017). Intravenous administration of G, galanin fragment WTLNSA-GYLLGPHA-OH or pharmacological agonist of G receptors WTLNSAGYLLGPβAH-OH to rats after occlusion of coronary artery decreased the formation of the spin adducts of hydroxyl radicals and TBARS in the area at risk during reperfusion . ...
The neuropeptide galanin (G) and its N-terminal fragments reduce the formation of reactive oxygen species and normalize myocardial metabolic and antioxidant state in experimental cardiomyopathy and ischemia/reperfusion injury. This study intends to elucidate the cardioprotective effect of G in rats treated with streptozotocin (STZ). The rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2) was prepared by the solid phase peptide synthesis using the Fmoc-strategy and purified by preparative HPLC. Its chemical structure was identified by ¹H-NMR spectroscopy and MALDI-TOF mass spectrometry. The animals were divided in four groups: C—normal control; S—STZ control, a single i.p. injection of STZ (35 mg/kg); SG—a single i.p. injection of STZ (35 mg/kg) and i.p. injections of G (5 nmol/kg/day for 4 weeks); and G—normal animals treated with G (5 nmol/kg/day for 4 weeks). Treatment with G prevented hyperglycemia in STZ rats. G significantly improved maximal ADP-stimulated respiration and respiratory control ratio in saponin-skinned myocardial fibers in SG group compared to S group. G enhanced myocardial metabolic state in animals treated with STZ by reducing ATP, phosphocreatine (PCr) and total creatine (ΣCr = PCr + Cr) losses, and decreasing lactate accumulation in parallel with elevation of glucose level. Administration of G reduced the increased activity of creatine kinase-MB and lactate dehydrogenase in blood plasma of STZ-treated rats. G also prevented the formation of STZ-induced lipid peroxidation products, thiobarbituric acid reactive substances, in blood plasma to a value not different from baseline. The results suggest that G may be a promising tool for reducing myocardial metabolic disorders in diabetes mellitus.
... As a key factor of the organic damage, the oxidative stress is associated with various diseases [18] , including CF [19] . Increased apoptosis and mitochondrial ROS production in hypoxic and deoxygenated cells reduce the exposure to short N-terminal gelatin fragments 2-15 [20] . The antioxidant has been shown to improve cardiac function and produce the antifibrosis effect [21,22] . ...
... The role of galanin receptors in diseases of the cardiovascular system is poorly understood. Recent studies have shown that exogenous N-terminal fragments of galanin WTLNSAGYLL-NH 2 (2-11) and WTLNSA-GYLLGPHA-OH (2-15) G1, which have a high affinity for the GalR2 receptor subtype, increased cell viability, inhibited apoptosis and the formation of superoxide radical anion and hydrogen peroxide in mitochondria of rat cardiomyoblast H9c2 cells during hypoxia-reoxygenation Pisarenko et al. 2017). To improve the solubility and proteolytic stability of galanin fragments, we synthesized a number of modified analogs of the G1 peptide preserving the pharmacophore amino acid residues responsible for binding to the GalR2 receptor. ...
Natural and chemically modified N-terminal galanin fragments (WTLNSAGYLLGPHA-OH (G1) and WTLNSAGYLLGPβAH-OH (G2), respectively) reduce functional and metabolic disturbances in the heart during experimental ischemia and reperfusion. The aim of this work was to examine whether these peptides and full-length rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, G3) decrease the formation of reactive oxygen species (ROS) and lipid peroxidation products in the heart with ischemia/reperfusion (I/R) injury. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experiments were performed on anaesthetized open-chest rats subjected to myocardial regional ischemia and reperfusion. The microdialysis method and the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin trap were used to monitor ROS content in the area at risk (AAR). Intravenous administration of G1, G2 or G3 after occlusion of coronary artery significantly decreased the content of DMPO-OH spin adduct in interstitium of the AAR during reperfusion compared to the control. These effects were accompanied by limitation of infarct size, reduction of the plasma activity of creatine kinase-MB and lactate dehydrogenase, and better preservation of the energy state of the AAR. In addition, peptides G2 and G3 significantly reduced the formation of thiobarbituric acid reactive substances in the AAR. The overall protective action of the peptides decreased in the order G2 > G3 > G1. The results suggest that pharmacological agonists of galanin receptors can be considered as promising agents to reduce oxidative stress in myocardial I/R injury.
... Gal expression has shown to undergo ischemia-related increase in the hippocampal neurons and protects these neurons from damage by opening up potassium channels [33]. Similarly, treatment with Gal fragments increased the cell viability and inhibited cell apoptosis and excessive mitochondrial ROS in cardiomyoblasts exposed to hypoxic stress [20,34]. Hence, Gal was a valid candidate for our study of lung ischemic reperfusion. ...
Lung ischemia reperfusion (IR) is known to occur after lung transplantation or cardiac bypass. IR leads to tissue inflammation and damage and is also associated with increased morbidity and mortality. Various receptors are known to partake in activation of the innate immune system, but the downstream mechanism of tissue damage and inflammation is yet unknown. MicroRNAs (miRNAs) are in the forefront in regulating ischemia reperfusion injury and are involved in inflammatory response. Here, we have identified by high-throughput approach and evaluated a distinct set of miRNAs that may play a role in response to IR in rat lung tissue. The top three differentially expressed miRNAs were validated through quantitative PCRs in the IR rat lung model and an in vitro model of IR of hypoxia and reoxygenation exposed type II alveolar cells. Among the miRNAs, miR-18a-5p showed consistent downregulation in both the model systems on IR. Cellular and molecular analysis brought to light a crucial role of this miRNA in ischemia reperfusion. miR-18a-5p plays a role in IR-mediated apoptosis and ROS production and regulates the expression of neuropeptide Galanin. It also influences the nuclear localization of transcription factor: nuclear factor-erythroid 2-related factor (Nrf2) which in turn may regulate the expression of the miR-18a gene. Thus, we have not only established a rat model for lung IR and enumerated the important miRNAs involved in IR but have also extensively characterized the role of miR-18a-5p. This study will have important clinical and therapeutic implications for and during transplantation procedures.
... INTRODUCTION (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and H-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-His-Ala-OH (2-15) (G1) inhibited apoptosis during hypoxia/reoxygenation of the isolated rat cardiomyocytes and cardiomyoblasts of the cell line H9c2 due to decrease in the production of superoxide anionradicals and hydrogen peroxide in mitochondria [2,3]. Both peptides promote metabolic and functional recovery of the rat heart after the damage induced by ischemia/reperfusion (I/R) ex vivo and in vivo. ...
... and H-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-His-Ala-OH (2-15) (G1) inhibited apoptosis during hypoxia/reoxygenation of the isolated rat cardiomyocytes and cardiomyoblasts of the cell line H9c2 due to decrease in the production of superoxide anionradicals and hydrogen peroxide in mitochondria [2,3]. Both peptides promote metabolic and functional recovery of the rat heart after the damage induced by ischemia/reperfusion (I/R) ex vivo and in vivo. ...
... The study of these peptides in the models of myocardial I/R injury revealed their cardiotropic properties [4]. It was demonstrated in the present work that the chimeric molecule of G2 containing the galanin sequence (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) supplemented by the natural dipeptide carnosine H-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-βAla-His-OH was the most effective [5]. Administration of the peptide G2 was shown to reduce heart dysfunction in rats with doxorubicin-induced cardiomyopathy [6]. ...
Antioxidant properties of rat galanin GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2 (Gal), N-terminal fragment of galanin (2-15 aa) WTLNSAGYLLGPHA (G1), and its modified analogue WTLNSAGYLLGPβAH (G2) were studied in vivo in the rat model of regional myocardial ischemia and reperfusion and in vitro in the process of Cu2+-induced free radical oxidation of human blood plasma low-density lipoproteins. Intravenous administration of G1, G2, and Gal to rats after ischemia induction reduced the infarction size and activities of the necrosis markers, creatine kinase-MB and lactate dehydrogenase, in blood plasma at the end of reperfusion. G1, G2, and Gal reduced formation of the spin adducts of hydroxyl radicals in the interstitium of the area at risk during reperfusion, moreover, G2 and Gal also reduced formation of the secondary products of lipid peroxidation in the reperfused myocardium. It was shown in the in vivo experiments and in the in vitro model system that the ability of galanin peptides to reduce formation of ROS and attenuate lipid peroxidation during myocardial reperfusion injury was not associated directly with their effects on activities of the antioxidant enzymes of the heart: Cu,Zn-superoxide dismutase, catalase, and glutathione peroxidase. The peptides G1, G2, and Gal at concentrations of 0.01 and 0.1 mM inhibited Cu2+-induced free radical oxidation of human low-density lipoproteins in vitro. The results of oxidative stress modeling demonstrated that the natural and synthetic agonists of galanin receptors reduced formation of the short-lived ROS in the reperfused myocardium, as well as of lipid radicals in blood plasma. Thus, galanin receptors could be a promising therapeutic target for cardiovascular diseases.
... Post-ischaemic administration of the peptides improved functional recovery of isolated perfused rat hearts and reduced infarct size in rats in vivo. 4,5 The chimeric ligand [βAla14, His15]-galanin (2-15) (G1), which is composed of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and the dipeptide carnosine, exhibited the most beneficial effect. 3 The mechanisms of action of peptide G1 remain unclear. ...
... Post-ischaemic administration of the peptides improved functional recovery of isolated perfused rat hearts and reduced infarct size in rats in vivo. 4,5 The chimeric ligand [βAla14, His15]-galanin (2-15) (G1), which is composed of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and the dipeptide carnosine, exhibited the most beneficial effect. 3 The mechanisms of action of peptide G1 remain unclear. ...
... Peptide G1 was designed as a hybrid linear molecule consisting of two parts sequentially connected by an amide bond. 3 The N-terminal part is a fragment of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and the C-terminal part is the other bioactive dipeptide L-carnosine capable of scavenging hydroxyl radicals (Table 1). 6 A fragment of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) contains residues Trp, 2 Asn, 5 Gly 8 and Tyr, 9 which are necessary for interaction of the peptide with the GalR2 receptor 7,8 and thereby to trigger cardioprotective effects. ...
The mechanisms of protective action of the neuropeptide galanin and its N‐terminal fragments against myocardial ischaemia/reperfusion (I/R) injury remain obscure. The aim of this work was to study effects of a novel peptide agonist of galanin receptors [βAla14, His15]‐galanin (2‐15) (G1) and the full‐length galanin (G2) on energy and antioxidant status of the heart with acute infarction. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1H‐NMR spectroscopy and MALDI‐TOF mass spectrometry. Experiments were performed on anaesthetized open‐chest rats subjected to myocardial regional ischaemia and reperfusion. Intravenous (iv) administration of optimal doses of peptides G1 and G2 (1.0 and 0.5 mg/kg, respectively) at the onset of reperfusion significantly reduced infarct size (on average by 40% compared with control) and the plasma activity of creatine kinase‐MB (CK‐MB) and lactate dehydrogenase (LDH). These effects were associated with augmented preservation of aerobic energy metabolism, increased activity of Cu,Zn superoxide dismutase (Cu,Zn‐SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px) and decreased lipid peroxidation in the area at risk (AAR) at the end of reperfusion. Peptide G1 showed more efficient recovery of the majority of metabolic and antioxidant parameters. The results provide evidence that the galaninergic system can be considered a promising target to reduce energy dysregulation and oxidative damage in myocardial I/R injury. This article is protected by copyright. All rights reserved.
... We have recently shown that natural and modified N-terminal fragments of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) reduce experimental myocardial I/R injury [21,22]. They are able to increase cell viability and inhibit apoptosis and mitochondrial ROS formation in rat H9c2 cardiomyoblast cells subjected to hypoxia-reoxygenation [21,23]. Postischemic infusion of these peptides improves functional recovery of isolated rat heart during reperfusion, reduces cell membrane damage, and enhances restoration of myocardial energy state. ...
... Postischemic infusion of these peptides improves functional recovery of isolated rat heart during reperfusion, reduces cell membrane damage, and enhances restoration of myocardial energy state. Intravenous administration of the peptides limits myocardial infarct size and decreases activity of necrosis markers in rats in vivo [21][22][23]. The beneficial effects of these peptide ligands are probably associated with activation of the GalR2 receptor, since they have a poor affinity for the receptor subtypes GalR1 and GalR3 [24]. ...
... A chimeric peptide G was synthesized by conjugation of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) with the dipeptide carnosine. When designing this peptide ligand, the following considerations have been taken into account: (i) the first 15 amino acid residues of N-terminal galanin fragments are of critical importance for their biological activity and cardiovascular regulation [35]; (ii) the deletion of the Gly1 residue results in loss of affinity of N-terminal galanin fragments for the GalR1 receptor [36]; (iii) galanin fragments (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) having preferential affinity for the GalR2 receptor are able to reduce I/R injury due to antioxidant properties and inhibition of cell death [21,23]; (iv) the Trp2 and Tyr9 residues, together with Asn5, Gly8, Leu10, and Gly12, are the critical pharmacophores for selective binding of galanin fragments to the GalR2 receptor [37]; (v) a novel agonist should be readily soluble in water to test its activity in animal models in vivo. The synthesized ligand G, [βAla14, His15]-galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), has a greater solubility in water than the natural galanin fragments (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) [22] and enhanced resistance to the action of exopeptidases due to carnosine tailing to C-terminal part of the molecule. ...
The clinical use of antineoplastic agent doxorubicin (DOX) is limited due to its cardiotoxic action. [βAla14, His15]-galanine (2–15) (G) is a novel synthetic agonist of galanin receptors GalR1-3 having cardioprotective properties in animal models in vivo. The aim of the present study was to explore effects of G on DOX-induced cardiotoxicity. Wistar rats were divided into four groups and treated with DOX (D group), DOX and G (D + G group), G (G group), and saline (control). Before treatment and at the end of the study, concentration of thiobarbituric acid reactive substances (TBARS) and activity of creatine kinase-MB (CK-MB) were determined in blood plasma, the animals were weighed, and cardiac function was evaluated by echocardiography. At the end of experiments, the hearts were used to determine energy metabolites and mitochondrial respiration in permeabilized fibers. After an 8-week study, D group exhibited a pronounced cardiac failure, the absence of weight gain, an increased plasma TBARS concentration, and CK-MB activity. These disorders were accompanied by a reduced myocardial content of high-energy phosphates and mitochondrial respiratory parameters. Co-administration of G with DOX significantly decreased plasma TBARS level and prevented an increase in plasma CK-MB activity. In D + G group, myocardial contents of ATP, PCr, total adenine nucleotides, and total creatine as well as myocardial PCr/ATP ratio and the respiratory control index were higher than in D group at the end of the experiments. Peptide G significantly improved parameters of left ventricular (LV) function and caused weight gain in animals of D + G group. These results suggest that peptide G may be a potential pharmacological agent that attenuates the cardiotoxic effects of DOX.
... Há algumas evidências de que o estresse oxidativo está envolvido na apoptose causada por isquemia e reperfusão. 13,14 Neste experimento, também descobrimos que o nível do conteúdo de MDA e a atividade da SOD estavam intimamente relacionados à razão de Bcl-2/Bax no tecido pulmonar. Tanto Bcl-2 quanto Bax pertencem à família de proteínas Bcl-2 e foram identificados como um dos principais fatores no início da apoptose. ...
Background and objectives:
Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats.
Methods:
Male Sprague-Dawley rats were randomly divided into four groups (n=8): control group, hemorrhagic shock group, 5ug.kg-1 dexmedetomidine (DEX1) group, and 10ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20min. 30min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue.
Results:
Compare with hemorrhagic shock group, 5ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25±0.24 vs. 4.12±0.42%, p<0.05), histological score (1.06±0.12 vs. 1.68±0.15, p<0.05) and protein (1.92±0.38 vs. 3.95±0.42mg.mL-1, p<0.05) and WBC (0.42±0.11 vs. 0.92±0.13×109/L, p<0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35±0.68 vs. 4.73±0.44U.mg-1 protein, p<0.05) and decreased malondialdehyde (2.18±0.19 vs. 3.28±0.27nmoL.mg-1 protein, p<0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55±0.04 vs. 0.34±0.05, p<0.05) and decreased the level of Bax (0.46±0.03 vs. 0.68±0.04, p<0.05), caspase-3 (0.49±0.03 vs. 0.69±0.04, p<0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p>0.05).
Conclusion:
Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.
