scholarly journals Irbesartan ameliorate inflammatory responses, and apoptosis induced by myocardial ischemia/reperfusion in male rats

2019 ◽  
Vol 7 (2) ◽  
pp. 138-150
Author(s):  
Najah R. Hadi ◽  
Fadhil G. Al-Amran
Keyword(s):  
Myocardial Ischemia ◽  
Troponin I ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Male Rats ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia–reperfusion (I-R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. This study was undertaken to investigate the potential role of Irbesartan in amelioration of myocardial I/R injury induced by ligation of coronary artery (LAD) in a rat model. We are pretreated the animals with Irbesartan 3mg/kg i.p. 30 minutes before ligation of LAD. At the end of experiment (2 h of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I (cTn-I). Compared with the sham group, levels of myocardial TNF-α, IL-1β, IL-6, MCP-1, MIP-1 alpha, and plasma cTn-I were increased (P<0.05). Histologically, all rats in control group showed significant cardiac injury after I-R. Furthermore, rats in control group showed significant apoptosis. Irbesartan significantly counteract the increased in myocardium level of TNF-α, IL-1B, IL-6, MCP-1, MIP-1 alpha, plasma cTn-I and apoptotosis (P<0.05). Histological analysis revealed that Irbesartan markedly reduced the severity of heart injury in the rats underwent LAD ligation procedure. We concluded that Irbesartan may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which induced by I/R injury.

scholarly journals The cardioprotective potential of Tadalafil in myocardial ischemia/reperfusion

2020 ◽  
Vol 8 (2) ◽  
pp. 87-100
Author(s):  
Najah R. Hadi ◽  
Fadhil G. Al-Amran
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Male Rats ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion

The objective of this study is to assess the potential protective effect of Tadalafil on myocardial ischemia reperfusion injury induced by LAD ligation, 28 male rats were randomized into 4 groups (7 rats per group); Sham, rats underwent the same anesthetic and surgical procedure except for LAD ligation; control, rats underwent LAD ligation for 30 minutes and reperfusion for 2 hours; vehicle, rats treated with 10% DMSO, the Tadalafil solvent 30 minutes before the ligation; Tadalafil group, rats pretreated with Tadalafil1mg/kg i.p 30 minutes before ligation. In control group, as compared with sham, tissue TNF-α, IL-6, IL-10, caspase-3 and BAX, plasma cTn-T and serum MDA significantly increased (P<0.05), while serum GSH significantly decreased (P<0.05). Histopathologically, control group showed a significant cardiac injury (P<0.05) compared with sham group. Tadalafil significantly counteracted (P<0.05) the increase of TNF-α, IL-6, caspase-3 and BAX and counteracted the increase in plasma cTn-T and serum MDA. Tadalafil produces a significant elevation (P<0.05) in cardiac IL-10 and serum GSH with significant reduction in (P<0.05) cardiac injury. In We concluded that Tadalafil attenuates myocardial I/R injury in male rats through interfering with inflammatory reactions and apoptosis .

scholarly journals ERK1/2-Egr-1 Signaling Pathway-Mediated Protective Effects of Electroacupuncture in a Mouse Model of Myocardial Ischemia-Reperfusion

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Juan Zhang ◽  
Jiangang Song ◽  
Jin Xu ◽  
Xuemei Chen ◽  
Peihao Yin ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Troponin I ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Protective Effects ◽  
Downstream Target ◽  
Myocardial Ischemia Reperfusion

Early growth response- (Egr-) 1 is an upstream master switch in controlling inflammatory responses following myocardial ischemia-reperfusion (I/R). Activation of extracellular signal-regulated protein kinase-1 and kinase-2 (ERK1/2) signaling is known to upregulate Egr-1. ERK1/2 pathway has been previously shown to mediate the therapeutic action of electroacupucture (EA). Thus, we hypothesized that EA would reduce myocardial I/R injury and inflammatory responses through inhibiting Egr-1 expression via the ERK1/2 pathway. Mice were pretreated with EA, U0126, or combination of EA and U0126 and then underwent 1 h myocardial ischemia and 3 h reperfusion. We investigated that EA significantly attenuated the I/R-induced upregulation of both Egr-1 and phosporylated-ERK1/2 (p-ERK1/2), decreased myocardial inflammatory cytokines including tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β), and reduced the infarct size and the release of cardiac troponin I (cTnI). U0126 treatment also exhibited the same effect as EA on Egr-1 level and subsequent cardioprotective effects. There was no additive effect of cotreatment with EA and U0126 on the expression of Egr-1 and its downstream target genes (TNF-α, IL-1β) or serum cTnI level. Collectively, these observations suggested that EA attenuates myocardial I/R injury, possibly through inhibiting the ERK1/2-Egr-1 signaling pathway and reducing the release of proinflammatory cytokines.

Astragaloside attenuates cardiotoxicity effects of Doxorubicin by inhibiting TLR4/NF-кB signaling pathway

2017 ◽  
Vol 5 (1) ◽  
pp. 78-92
Author(s):  
Najah R. Hadi ◽  
Fadhil G. Al-Amran
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Protective Effect ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Ischemic Tissue ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion ◽  
Significant Protective Effect

Myocardial Ischemia-Reperfusion (I/R) injury refers to myocardial, vascular or electrophysiological dysfunction of heart induced by the restoration of blood flow to previously ischemic tissue. In this study, we investigated the effects of Telmisartan in I/R injury and apoptosis. Mice are subjected to 30 min ischemia followed by 120 min reperfusion through ligation of descending coronary artery (LAD). Mice treated with Telmisartan (0.5mg/kg, via IP injection) significantly attenuated I/R-induced increases of myocardial TNF-α, IL-1β, IL-6 and markedly increased myocardial Bcl-2 protein expression. Furthermore, Telmisartan significant protective effect against myocardial I/R injury. These results demonstrated that Telmisartan reduces inflammatory reaction associated with I/R injury induced by LAD ligation in addition to its reduction for cardiac injury and apoptosis induced by ischemia reperfusion.

Abstract 385: Amelioration of Heart Transplantation-Induced Ischemia-Reperfusion Injury by Melatonin and Ghrelin in Rats

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Fadhil Alamran
Keyword(s):  
Heart Transplantation ◽  
Sham Group ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Heterotopic Heart Transplantation ◽  
Tnf Α ◽  
Transplant Procedure

Background: Global myocardial ischemia reperfusion (I/R), which is often obligatory during cardiac surgery, induce an inflammatory response in the transplanted heart. Inflammatory reactions in the graft have a pivotal influence on acute as well as long term graft function. Objective: This study was undertaken to investigate the potential role of melatonin and ghrelin in amelioration of I/R injury in the transplanted heart in rat model. Materials and Methods: The rats were randomized into 4 equal groups. Group 1 sham group, rat underwent the same anesthetic and surgical procedure as the control group except for heterotopic heart transplantation, group 2 control group, rats underwent heterotopic heart transplantation and subjected to global ischemia for 30 min and reperfusion for 2 hours, group 3 donor and recipient rats received melatonin 10 mg/kg i.p. 30 min before the transplant procedure and the same dose at the reperfusion, group 4 donor and recipient rats received ghrelin 10 -8 mol/kg i.p. ( 2 doses) 13 & 1 hour before the transplant procedure, the heterotopic heart transplantation is done using the cuff technique in the neck ( the aorta of the donor is anastomosed with the carotid artery of the recipient and the pulmonary artery of the donor to the jugular vein of the recipient). At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I(cTn I). The heart were harvested, the apical side was fixed in 10% formalin for histological examination and the basal side was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and intracellular adhesion molecule-1 (ICAM-1). Results: Compared with the sham group, levels of myocardial TNF-α & IL-1β, and ICAM-1; plasma cTn I were increased (p<0.05), Histologically, all induced untreated rats showed significant myocardial injury ( P < 0.05) Both melatonin and ghrelin significantly counteract the increase in myocardium level of TNF-α, IL-1, & ICAM-1 ( P < 0.05). histological analysis revealed that both melatonin and ghrelin markedly reduced ( P < 0.05) the severity of heart injury in the rats underwent transplant procedure. Conclusion: The results of the present study reveal that melatonin and ghrelin may ameliorate I/R injury in the grafted heart in rats via interfering with inflammatory reactions which induced by I/R injury . These findings suggested that both melatonin and ghrelin have a promising graft protective effect against transplant induced global I/R injury.

scholarly journals Both Castration and Goserelin Acetate Ameliorate Myocardial Ischemia Reperfusion Injury and Apoptosis in Male Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Najah R. Hadi ◽  
Fadhil G. Yusif ◽  
Maitham Yousif ◽  
Karrar K. Jaen
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Sham Group ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Control Group ◽  
Goserelin Acetate ◽  
Myocardial Ischemia Reperfusion

Although reperfusion of an ischemic organ is essential to prevent irreversible tissue damage, it may amplify tissue injury. This study investigates the role of endogenous testosterone in myocardial ischemia reperfusion and apoptosis in male rats. Material and method. Twenty four male rats were randomized into 4 equal groups: Group (1), sham group, rats underwent the same anesthetic and surgical procedure as the control group except for LAD ligation; Group (2), Active control group, rats underwent LAD ligation; Group (3), castrated, rats underwent surgical castration, left 3wks for recovery, and then underwent LAD ligation; and Group (4), Goserelin acetate treated, rats received 3.6 mg of Goserelin 3 wks before surgery and then underwent LAD ligation. At the end of experiment, plasma cTn I, cardiac TNF-α, IL1-β, ICAM-1, and Apoptosis level were measured and histological examination was made. Results. Compared to sham group, the levels of myocardial TNF-α, IL-1β, ICAM-1, apoptosis, and plasma cTn I were significantly increased (P<0.05) in control group and all rats showed significant myocardial injury (P<0.05). Castration and Goserelin acetates significantly counteract the increase in myocardial levels of TNF-α, IL-1β, ICAM-1, plasma cTn I, and apoptosis (P<0.05) and significantly reduce (P<0.05) the severity of myocardial injury. We conclude that castration and Goserelin acetates ameliorate myocardial I/R injury and apoptosis in rats via interfering with inflammatory reactions.

scholarly journals Effects of Thyroid Hormone Analogue and a Leukotrienes Pathway-Blocker on Reperfusion Injury Attenuation after Heart Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Fadhil G. Al-Amran ◽  
Najah R. Hadi ◽  
Haider S. H. Al-Qassam
Keyword(s):  
Myocardial Ischemia ◽  
Heart Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Control Group ◽  
Group I ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-α, IL-1β, and ICAM-1 and plasma level of cTnI (). Morphologic analysis showed that both MK-886 and DITPA markedly improved () the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.

scholarly journals Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice

2018 ◽  
Vol 49 (4) ◽  
pp. 1476-1491 ◽  
Author(s):  
Shu-Bo  Zhang ◽  
Tie-Jun Liu ◽  
Guo-Hua Pu ◽  
Bao-Yong Li ◽  
Xiao-Zeng Gao ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Myocardial Cells ◽  
Non Coding Rna ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion ◽  
Pka Pathway ◽  
Long Non Coding Rna

Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected. Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. Conclusion: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.

Abstract 316: Role of an Inflammasome Adaptor Molecule ASC (Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain) in Myocardial Ischemia-Reperfusion Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masanori Kawaguchi ◽  
Masafumi Takahashi ◽  
Takeki Hata ◽  
Yasuko Takahashi ◽  
Hajime Morimoto ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Caspase Recruitment Domain ◽  
Lv Dysfunction ◽  
Infarct Area ◽  
Injured Myocardium ◽  
Myocardial Ischemia Reperfusion

Inflammatory responses play a key role in the pathophysiology of myocardial ischemia-reperfusion (I/R) injury. ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) is an adaptor protein that forms “inflammasome” whose activation leads to caspase-1-dependent interleukin (IL)-1β generation and subsequent inflammatory responses; however, the role of ASC in myocardial I/R injury remains unclear. Baseline left ventricular (LV) function was unaltered in ASC-deficient (ASC −/− ) mice. ASC −/− (n=42) and wild-type control (WT) (n=42) mice were subjected to 30 min LAD occlusion, followed by reperfusion. ASC −/− mice showed reduced infarct area (infarct area/area at risk: 18.7% vs. 28.6% at 48 h, p< 0.01) and scar formation (scar/LV area: 9.7% vs. 14.6% at 14 days, p< 0.01) after myocardial I/R. Echocardiography showed improved LV dysfunction (%FS: 35.2 vs. 28.4 at 7 days, p< 0.01; 34.0 vs. 25.7 at 14 days, p< 0.01) and dimensions (LVEDD [mm]: 3.88 vs. 4.21 at 7 days, p< 0.01; 3.99 vs. 4.43 at 14 days, p< 0.01) in the ASC −/− mice after myocardial I/R. Immunohistochemistry revealed that infiltration of macrophages (Mac3) and neutrophils (Gr-1) was markedly decreased in the injured myocardium of the ASC −/− mice (48 hr [/mm 2 ]: 1226 vs. 884, p< 0.01; 782 vs. 554, p< 0.01, respectively); however, there was no difference of neovascularization (CD31) in the ischemic area. Double immunofluorescent staining showed that ASC expression was clearly observed in the infiltrated macrophages and neutrophils in the injured myocardium. Real-time RT-PCR analysis demonstrated that the myocardial expression of inflammatory cytokines, such as IL-1β, IL-6, and MCP-1, after I/R were significantly decreased in the ASC −/− mice, compared to that in the WT mice. Further, in vitro experiments showed that LPS-induced production of these inflammatory cytokines in the ASC −/− bone marrow cells was significantly decreased. These findings demonstrate that ASC deficiency prevents inflammatory cell infiltration and cytokine expression, thereby resulting in the improvement of LV dysfunction and remodeling after myocardial I/R injury, and suggest that ASC is a novel therapeutic target for myocardial I/R injury.

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