Cardioprotective Effects of Glatiramer Against Ischemia- Reperfusion Injury in Coronary Artery Ligation Model in Rats Through Activation of AKT-GSK-3β-TNF-α-Nrf2 Signalling Pathway

2022 ◽  
Vol 18 (1) ◽  
pp. 79-86
Author(s):  
Zhulin Zhang ◽  
Xiurui Ma ◽  
Guanrui Yang ◽  
Lizhen Zhang
Keyword(s):  
Coronary Artery ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Signalling Pathway ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Gsk 3Β

scholarly journals Huang Qi Tong Bi Decoction Attenuates Myocardial Ischemia-Reperfusion Injury via HMGB1/TLR/NF-κB Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Kun Liu ◽  
Manman Li ◽  
Xiumei Ren ◽  
Qing-sheng You ◽  
Fei Wang ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
St Segment ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

The aim of this study was to study the protective effect of Huang Qi Tong Bi Decoction (HQTBT) on the heart of rats. Ischemia-reperfusion injury was established by coronary artery ligation. Proinflammatory cytokines were decreased by XFZY in coronary artery ligated rats. ST segment was also restored with the treatment of HQTBT. Triphenyltetrazole chloride (TTC) staining and pathological analysis showed that HQTBT reduced myocardial injury. Besides, the expressions of HMGB1/TLR/NF-κB pathway in rats were significantly decreased by HQTBT. This study shows that HQTBT inhibited inflammatory reaction on myocardial injury in rats.

scholarly journals Febuxostat Modulates MAPK/NF-κBp65/TNF-α Signaling in Cardiac Ischemia-Reperfusion Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Sana Irfan Khan ◽  
Rajiv Kumar Malhotra ◽  
Neha Rani ◽  
Anil Kumar Sahu ◽  
Ameesha Tomar ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Morphological Alterations ◽  
Treatment Groups ◽  
Antiapoptotic Proteins ◽  
Male Wistar Rats

Xanthine oxidase and xanthine dehydrogenase have been implicated in producing myocardial damage following reperfusion of an occluded coronary artery. We investigated and compared the effect of febuxostat and allopurinol in an experimental model of ischemia-reperfusion (IR) injury with a focus on the signaling pathways involved. Male Wistar rats were orally administered vehicle (CMC) once daily (sham and IR + control), febuxostat (10 mg/kg/day; FEB10 + IR), or allopurinol (100 mg/kg/day; ALL100 + IR) for 14 days. On the 15th day, the IR-control and treatment groups were subjected to one-stage left anterior descending (LAD) coronary artery ligation for 45 minutes followed by a 60-minute reperfusion. Febuxostat and allopurinol pretreatment significantly improved cardiac function and maintained morphological alterations. They also attenuated oxidative stress and apoptosis by suppressing the expression of proapoptotic proteins (Bax and caspase-3), reducing TUNEL-positive cells, and increasing the level of antiapoptotic proteins (Bcl-2). The MAPK-based molecular mechanism revealed suppression of active JNK and p38 proteins concomitant with the rise in ERK1/ERK2, a prosurvival kinase. Additionally, a reduction in the level of inflammatory markers (TNF-α, IL-6, and NF-κB) was also observed. The changes observed with febuxostat were remarkable in comparison with those observed with allopurinol. Febuxostat protects relatively better against IR injury than allopurinol by suppressing inflammation and apoptosis mediating the MAPK/NF-κBp65/TNF-α pathway.

scholarly journals Effectiveness ofPanax ginsengon Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Luo Pei ◽  
Hou Shaozhen ◽  
Dong Gengting ◽  
Chen Tingbo ◽  
Liu Liang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Panax Ginseng ◽  
Testosterone Level ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Protective Mechanisms ◽  
Artery Ligation ◽  
Measured Time ◽  
Myocardial Ischemia Reperfusion

Mechanisms forPanax ginseng’s cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardizedPanax ginsengextract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE’s effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability ofPanax ginsengto protect the heart from myocardial I/R injury.

scholarly journals Autophagic Flux Impairment Exacerbates Myocardial Ischemia-Reperfusion Injury in Experimental Diabetes Through Atg5/LAMP2 Cleavage by Calpains

2020 ◽  
Author(s):  
Lichun Guan ◽  
Ziqin Yu ◽  
Zhimei Che ◽  
Hang Zhang ◽  
Yong Yu ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Heart ◽  
Autophagic Flux ◽  
Coronary Artery Ligation ◽  
Negative Effects ◽  
Artery Ligation ◽  
R Process ◽  
Myocardial Ischemia Reperfusion

Abstract Background: is a chronic metabolic disease characterized by hyperglycemia, which has negative effects on cardiac revascularization in patients with coronary artery disease (CAD). Methods: This study focused on the role of autophagic flux in regulating susceptibility of STZ-induced diabetic heart to ischemia-reperfusion (I/R) injury. We established STZ-induced diabetes mice and perform I/R process by coronary artery ligation, and neonatal mice cardiomyocytes culture subjected to high glucose and hypoxia/reoxygenation(H/R). Results: Diabetic heart was more sensitive to I/R injury. Autophagic flux, represented by TEM, relative LC3Ⅱ changes under CQ intervention and P62 expression, was impaired in diabetic hearts and deteriorated during subsequent I/R. Calpains were activated in diabetic I/R heart, and the inhibition of calpains partially rescued autophagic flux, cardiac function, and cell death. The expression of autophagic flux related proteins Atg5 and LAMP2 decreased significantly in diabetic I/R heart. Further studies suggested that calpain could cleave Atg5 and LAMP2, and generate cleaved fragments, which might be reversed by calpain inhibition. Inhibition of calpain，or in company with overexpression of Atg5 and LAMP2 , could reduce myocardial injury in diabetic heart subject to I/R. But overexpression of Atg5 alone could worsen the I/R injury. Conclusion: In conclusion, calpain-mediated cleavage of Atg5 and LAMP2 accounts for the impaired autophagic flux which increases the susceptibility to myocardial I/R injury in experimental diabetic mice.

scholarly journals Mechanisms of ranolazine pretreatment in preventing ventricular tachyarrhythmias in diabetic db/db mice with acute regional ischemia–reperfusion injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chung-Chuan Chou ◽  
Hui-Ling Lee ◽  
Gwo-Jyh Chang ◽  
Hung-Ta Wo ◽  
Tzung-Hai Yen ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Ventricular Tachyarrhythmias ◽  
Artery Ligation ◽  
Electrophysiological Studies ◽  
Myocardial Ischemia Reperfusion

AbstractStudies have demonstrated that diabetic (db/db) mice have increased susceptibility to myocardial ischemia–reperfusion (IR) injury and ventricular tachyarrhythmias (VA). We aimed to investigate the antiarrhythmic and molecular mechanisms of ranolazine in db/db mouse hearts with acute IR injury. Ranolazine was administered for 1 week before coronary artery ligation. Diabetic db/db and control db/+ mice were divided into ranolazine-given and -nongiven groups. IR model was created by 15-min left coronary artery ligation and 10-min reperfusion. In vivo electrophysiological studies showed that the severity of VA inducibility was higher in db/db mice than control (db/ +) mice. Ranolazine suppressed the VA inducibility and severity. Optical mapping studies in Langendorff-perfused hearts showed that ranolazine significantly shortened action potential duration, Cai transient duration, Cai decay time, ameliorated conduction inhomogeneity, and suppressed arrhythmogenic alternans induction. Western blotting studies showed that the expression of pThr17-phospholamban, calsequestrin 2 and voltage-gated sodium channel in the IR zone was significantly downregulated in db/db mice, which was ameliorated with ranolazine pretreatment and might play a role in the anti-arrhythmic actions of ranolazine in db/db mouse hearts with IR injury.

Mechanisms of Ranolazine Pretreatment in Preventing Ventricular Tachyarrhythmias in Diabetic db/db Mice with Acute Regional Ischemia-Reperfusion Injury

2020 ◽  
Author(s):  
Chung-Chuan Chou ◽  
Hui-Ling Lee ◽  
Gwo-Jyh Chang ◽  
Hung-Ta Wo ◽  
Tzung-Hai Yen ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Decay Time ◽  
Molecular Mechanisms ◽  
Optical Mapping ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Ventricular Tachyarrhythmias ◽  
Artery Ligation

Abstract Background: Studies have demonstrated that db/db mice have increased susceptibility to myocardial ischemia-reperfusion (IR) injury and ventricular tachyarrhythmias (VA). We aimed to investigate the antiarrhythmic and molecular mechanisms of ranolazine in db/db mouse hearts with acute IR injury.Methods: Ranolazine was administered for 1 week before coronary artery ligation. Diabetic db/db and control db/+ mice were divided into ranolazine-given and -nongiven groups. IR model was created by 15-min left coronary artery ligation and 10-min reperfusion. In vivo electrophysiological studies and optical mapping to simultaneously record intracellular Ca2+ (Cai) and membrane voltage in Langendorff-perfused hearts were performed. Western blotting and whole-cell patch clamp study were performed to evaluate the effect of ranolazine in the non-IR and IR zones. Results: The severity of VA inducibility by burst pacing was higher in db/db mice than db/+ mice with acute IR injury. Ranolazine suppressed VA inducibility and severity in db/db and db/+ mice. Optical mapping studies showed that ranolazine significantly shortened action potential duration (APD80), Cai transient duration (CaiTD80), Cai decay time, ameliorated conduction inhomogeneity, and suppressed arrhythmogenic alternans induction. The expression of pThr17-phospholamban, calsequestrin 2 and SCN5A in the IR zone was significantly downregulated in db/db mice, which was ameliorated by ranolazine. Conclusions: Ranolazine pretreatment shortens APD80 and CaiTD80, reduces Cai decay time, and ameliorates conduction velocity inhomogeneity to suppress induction of arrhythmogenic alternans and VA; and amelioration of downregulation of pThr17-phospholamban, calsequestrin 2 and SCN5A may partly underlie the anti-arrhythmic molecular mechanisms of ranolazine in db/db mouse hearts with IR injury.

Regulation of phosphatase and tensin homolog on chromosome 10 in response to hypoxia

2012 ◽  
Vol 302 (9) ◽  
pp. H1806-H1817 ◽  
Author(s):  
Jinqiao Qian ◽  
Shukuan Ling ◽  
Alexander C. Castillo ◽  
Bo Long ◽  
Yochai Birnbaum ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Chromosome 10 ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Phosphatase and tensin homolog on chromosome 10 (PTEN) is downregulated during hypertrophic and cancerous cell growth, leading to activation of the prosurvival Akt pathway. However, PTEN regulation in cardiac myocytes upon exposure to hypoxia remains unclear. We explored the role of PTEN in response to hypoxia/ischemia in the myocardium. We validated that PTEN is a transcriptional target of activating transcription factor 2 (ATF-2) and is positively regulated via a p38/ATF-2 signaling pathway. Accordingly, hypoxia-induced upregulation of phosphorylation of ATF-2 and PTEN were reversed by a dominant negative mutant p38. Inhibition of PTEN in cardiomyocytes attenuated hypoxia-induced cell death and apoptosis. Cardiac-specific knockout of PTEN resulted in increased phosphorylation of Akt and forkhead box O 1 (forkhead transcription factors), limited infarct size in animals exposed to ischemia-reperfusion injury, and ameliorated deterioration of left ventricular function and remodeling following permanent coronary artery occlusion. In addition, the activation of Bim, FASL, and caspase was coupled with PTEN activation, all of which were attenuated by PTEN inhibition. In conclusion, cardiomyocyte-specific conditional PTEN deletion limited myocardial infarct size in an in vivo model of ischemia-reperfusion injury and attenuated adverse remodeling in a model of chronic permanent coronary artery ligation.

scholarly journals Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway

2021 ◽  
Vol 12 (1) ◽  
pp. 020-031
Author(s):  
Kong Fu ◽  
Miancong Chen ◽  
Hua Zheng ◽  
Chuanzi Li ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

Sign in / Sign up

Export Citation Format

Share Document