Reciprocalcation of caveolin and HSP-72 on IPC interceded cardio-protection in the orchidectomized rats

2021 ◽  
Vol 12 (1) ◽  
pp. 683-689
Author(s):  
Ritesh Kumar Srivastav ◽  
Tarique Mahmood Ansari ◽  
Mahesh Prasad ◽  
Vishal Kumar Vishwakarma ◽  
Shravan Kumar Paswan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Male Rats ◽  
Oxidative Stress Marker ◽  
Myocardial Infarct Size ◽  
Perfused Heart ◽  
Oxidative Stress Parameter ◽  
Cardio Protection ◽  
And Oxidative Stress

Diminished testosterone levels conjoined to cardiovascular risk factor mainly myocardial infarction which broadens the risk of cardiovascular mortality referring to age. Ischemic preconditioning (IPC) is one of the interventions to shield such injury. The present study implicated the possible involvement of caveolin and heat shock protein 72 (HSP-72) during stress in orchidectomy (OCD) challenged rats. OCD was performed in male rats and kept for 6 weeks to observe the reduction in the level of testosterone. Isolated perfused heart of normal and OCD group was subjected to ischemic insult as per IPC cycle. Myocardial infarct size, haemodynamic, enzymatic and oxidative stress parameter were assessed for each heart. Diadzein (DDZ) a caveolin inhibitor was administered before the isolation of heart and it significantly decreases myocardial infarct size, release of lactate dehydrogenase, creatinine kinase and oxidative stress marker. DDZ also potentiated the effect IPC-mediated increase in the heart rate and coronary flow. The effect of caveolin inhibitor was remarkably reduced by quercetin administered before 1 h. of the administration DDZ. The findings of this study revealed that protection of myocardium induced by caveolin inhibitor pretreatment has not been lost in OCD rat heart.

scholarly journals Diabetes impairs the protective effects of sevoflurane postconditioning in myocardium subjected to ischemia/reperfusion injury in rats: important role of Drp1

2020 ◽  
Author(s):  
Jing Yu ◽  
Jiandong He ◽  
Wenqu Yang ◽  
Xiang Wang ◽  
Gaoxiang Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Myocardial Infarct Size ◽  
Diabetic Myocardium ◽  
Sevoflurane Postconditioning ◽  
And Oxidative Stress

Abstract Background Sevoflurane postconditioning (SevP) is an effective way in relieving myocardial ischemia/reperfusion (IR) injury, which doesn’t work well in diabetic myocardium unfortunately. Prior studies have noted the importance of increasing oxidative stress in diabetic tissues. Noteworthily, mitochondrial fission mediated by dynamin-related protein 1 (Drp1) is an upstream pathway of reactive oxygen production. Whether Drp1 dependent mitochondrial fission is associated with the ineffectiveness of SevP in diabetic myocardium remains unknown. The aim of this study was to explore the important role of Drp1 in diabetic myocardium and investigate whether Drp1 inhibition could restore the cardioprotective effect of SevP. Methods In the first part, adult male Sprague-Dawley(SD) rats were divided into 6 groups. Rats in diabetic groups were fed with high-fat and high-sugar for 8 weeks, and then received a injection of streptozotocin (35 mg/kg) intraperitoneally. Myocardial IR was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion༎SevP was applied by continuous inhalation of 2.5% sevoflurane 1 min before reperfusion, which lasted for 10 min. In the second part, mdivi-1 was used to investigate whether Drp1 inhibition could restore the cardioprotective effects of SevP in diabetic myocardium against I/R injury. The myocardial infarct size, pathology, mitochondrial ultrastructure, cardiomyocyte apoptosis, total SOD activity, MDA content, and Drp1 expression were detected. Results The diabetic myocardium displayed severer injury with greater infarct size and apoptosis. Up-regulated Drp1 expression concomitant with increased mitochondrial fission and oxidative stress were observed in diabetic myocardium subjected to I/R. The deteriorated changes were alleviated in normal but not in diabetic rats. Importantly, mdivi-1 administration significantly suppressed mitochondrial fission and oxidative stress, and the beneficial effects of SevP were restored by mdivi-1. Conclusions The present study indicates a crucial role of Drp1 dependent mitochondrial fission in diabetic myocardium subjected to IR. Drp1 inhibition may be effective in restoring the effect of SevP in reducing diabetic myocardial IR injury.

scholarly journals Hydralazine protects the heart against acute ischaemia/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission

2021 ◽  
Author(s):  
Siavash Beikoghli Kalkhoran ◽  
Janos Kriston-Vizi ◽  
Sauri Hernandez-Resendiz ◽  
Gustavo E Crespo-Avilan ◽  
Ayeshah A Rosdah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Mitochondrial Fission ◽  
Vehicle Control ◽  
Myocardial Infarct Size ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Pre Treatment ◽  
Apoptotic Effects

Abstract Aims Genetic and pharmacological inhibition of mitochondrial fission induced by acute myocardial ischaemia/reperfusion injury (IRI) has been shown to reduce myocardial infarct size. The clinically used anti-hypertensive and heart failure medication, hydralazine, is known to have anti-oxidant and anti-apoptotic effects. Here, we investigated whether hydralazine confers acute cardioprotection by inhibiting Drp1-mediated mitochondrial fission. Methods and results Pre-treatment with hydralazine was shown to inhibit both mitochondrial fission and mitochondrial membrane depolarisation induced by oxidative stress in HeLa cells. In mouse embryonic fibroblasts (MEFs), pre-treatment with hydralazine attenuated mitochondrial fission and cell death induced by oxidative stress, but this effect was absent in MEFs deficient in the mitochondrial fission protein, Drp1. Molecular docking and surface plasmon resonance studies demonstrated binding of hydralazine to the GTPase domain of the mitochondrial fission protein, Drp1 (KD 8.6±1.0 µM), and inhibition of Drp1 GTPase activity in a dose-dependent manner. In isolated adult murine cardiomyocytes subjected to simulated IRI, hydralazine inhibited mitochondrial fission, preserved mitochondrial fusion events, and reduced cardiomyocyte death (hydralazine 24.7±2.5% vs. control 34.1±1.5%, P=0.0012). In ex vivo perfused murine hearts subjected to acute IRI, pre-treatment with hydralazine reduced myocardial infarct size (as % left ventricle: hydralazine 29.6±6.5% vs. vehicle control 54.1±4.9%, P=0.0083), and in the murine heart subjected to in vivo IRI, the administration of hydralazine at reperfusion, decreased myocardial infarct size (as % area-at-risk: hydralazine 28.9±3.0% vs. vehicle control 58.2±3.8%, P<0.001). Conclusion We show that, in addition to its antioxidant and anti-apoptotic effects, hydralazine, confers acute cardioprotection by inhibiting IRI-induced mitochondrial fission, raising the possibility of repurposing hydralazine as a novel cardioprotective therapy for improving post-infarction outcomes.

scholarly journals Glycolipid RC-552 induces delayed preconditioning-like effect via iNOS-dependent pathway in mice

1999 ◽  
Vol 277 (6) ◽  
pp. H2418-H2424 ◽  
Author(s):  
Lei Xi ◽  
Fadi Salloum ◽  
Demet Tekin ◽  
Novlet C. Jarrett ◽  
Rakesh C. Kukreja
Keyword(s):  
Infarct Size ◽  
Knockout Mice ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Perfused Heart ◽  
Reduce Infarct Size ◽  
Monophosphoryl Lipid A ◽  
Dependent Pathway ◽  
Delayed Cardioprotection

We recently demonstrated that monophosphoryl lipid A (MLA)-induced delayed cardioprotection is mediated by inducible nitric oxide synthase (iNOS) in mice. In the present study, we determined whether RC-552, a novel synthetic glycolipid related in chemical structure to MLA, could afford similar protection. Adult mice were pretreated with vehicle or RC-552 (350 μg/kg ip, n = 7 mice/group) 24 h before global ischemia and reperfusion in a Langendorff isolated, perfused heart model. A group of RC-552-treated mice received S-methylisothiourea (SMT), a selective inhibitor of iNOS (3 mg/kg ip), 30 min before heart perfusion. Myocardial infarct size was significantly reduced from 19.2 ± 2.0% in vehicle to 8.2 ± 2.9% in RC-552 group ( P < 0.05). Treatment with SMT abolished RC-552-induced reduction in infarct size (20.0 ± 3.9%). In addition, RC-552 failed to reduce infarct size in isolated hearts from iNOS knockout mice (27.1 ± 2.8%) compared with that in hearts from control knockout mice without drug treatment (22.9 ± 5.4%). Acute buffer perfusion with RC-552 (0.1, 1.0, or 2.5 μg/ml) for 8 min immediately before ischemia-reperfusion did not reduce infarct size significantly. We concluded that RC-552 induces delayed cardioprotection via an iNOS-dependent pathway.

scholarly journals Thymoquinone dose-dependently attenuates myocardial injury induced by isoproterenol in rats via integrated modulation of oxidative stress, inflammation, apoptosis, autophagy and fibrosis

2021 ◽  
Author(s):  
Mahmoud Mohamed Farag ◽  
Asmaa Ahmed Khalifa ◽  
Wessam Fahmy El-Hadidy ◽  
Radwa Mohamed Rashad
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Cell Damage ◽  
Myocardial Infarct ◽  
Research Work ◽  
Radical Scavenging ◽  
Cardiac Biomarkers ◽  
Male Rats ◽  
Myocardial Infarct Size ◽  
Myocardial Oxidative Stress

Abstract As rats develop myocardial infarction (MI) like lesions when injected with large doses of isoproterenol (ISO), this investigation was designed to evaluate the effects of low and high doses of thymoquinone (TQ) on ISO-induced myocardial injury in rats. Adult male rats were divided into control, TQ20 (20 mg/kg/day), TQ50 (50 mg/kg/day), and ISO, TQ20 + ISO and TQ50 + ISO groups. In these rats, biochemical, immunobiochemical and histopathological studies were carried out to evaluate myocardial oxidative stress, inflammation, apoptosis, fibrosis and autophagy and serum cardiac biomarkers. The results showed that TQ pretreatment in ISO-administered rats produced a dose-dependent significant reduction of the myocardial infarct size, markedly reduced the ISO-induced elevation in serum cardiac markers and demonstrated several other important findings related to the cardioprotective efficacy of TQ. First, this study is the first reported research work showing that TQ treatment could increase the myocardial reduced glutathione baseline level, adding an indirect antioxidant effect to its known direct free radical scavenging effect. Second, pretreatment with TQ significantly reduced the markers of myocardial oxidative stress, inflammation, fibrosis and apoptosis. Third, TQ acted as an autophagy enhancer ameliorating myocardial cell damage and dysfunction. Thus, the changes associated with ISO-induced myocardial injury were ameliorated with TQ pretreatment. Additionally, the extent of observed improvement was significantly greater with the high TQ dose than with the low dose use. These findings raise the possibility that TQ may serve as a promising prophylactic cardioprotective therapy for patients who are at risk of developing myocardial injury as in cases of MI.

scholarly journals Remote Limb Ischaemic Postconditioning Protects Against Myocardial Ischaemia/Reperfusion Injury in Mice: Activation of JAK/STAT3-Mediated Nrf2-Antioxidant Signalling

2017 ◽  
Vol 43 (3) ◽  
pp. 1140-1151 ◽  
Author(s):  
Sumin Gao ◽  
Leyun Zhan ◽  
Zhengchao Yang ◽  
Ruili Shi ◽  
Haobo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Ischaemia ◽  
Nuclear Translocation ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Enzyme Release ◽  
Ischaemia Reperfusion ◽  
Myocardial Oxidative Stress ◽  
Creatine Kinase Mb

Background: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. Methods: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 min of reperfusion in the left hind limb at the start of the reperfusion period. After 2 h of cardiac reperfusion, myocardial infarct size, cardiac enzyme release, apoptosis and oxidative stress were assessed. Protein expression and phosphorylation were measured by Western blotting. Results: RIPostC significantly decreased cardiac IR injury, as reflected by reduced infarct size and cellular apoptosis (22.9 ± 3.3% vs 40.9 ± 6.2% and 13.4% ± 3.1% vs 26.2% ± 3.1%, respectively, both P < 0.01) as well as plasma creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release (21.97 ± 4.08 vs 35.86 ± 2.91 ng/ml and 6.17 ± 0.58 vs 8.37 ± 0.89 U/ml, respectively, both P < 0.01) compared with the IR group. RIPostC significantly increased the phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.01). In addition, RIPostC elevated the nuclear translocation of Nrf2 and the expression of HO-1 and reduced myocardial oxidative stress (P < 0.05). Interestingly, pretreatment with the JAK/STAT3 inhibitor AG490 blocked the cardioprotective effect of RIPostC accompanied by decreased phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.05), decreased nuclear translocation of Nrf2 and expression of HO-1, as well as increased oxidative stress (P < 0.05). Conclusion: RIPostC attenuates apoptosis and protects against myocardial IR injury, possibly through the activation of JAK/STAT3-mediated Nrf2-antioxidant signalling.

scholarly journals Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dong Wang ◽  
Xin Guo ◽  
Mingjie Zhou ◽  
Jichun Han ◽  
Bo Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Aqueous Extract ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion

This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE). The myocardial ischemia/reperfusion (I/R) injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP) and the maximum up/downrate of left ventricular pressure (±dp/dtmax) were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

Sex differences in myocardial infarct size are abolished by sarcolemmal KATP channel blockade in rat

2006 ◽  
Vol 290 (6) ◽  
pp. H2644-H2647 ◽  
Author(s):  
Micah S. Johnson ◽  
Russell L. Moore ◽  
David A. Brown
Keyword(s):  
At Risk ◽  
Sex Differences ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Female Rats ◽  
Male Rats ◽  
Myocardial Infarct Size ◽  
Sprague Dawley

This study was conducted to examine the relationship between myocardial ATP-sensitive potassium (KATP) channels and sex differences in myocardial infarct size after in vitro ischemia-reperfusion (I/R). Hearts from adult male and female Sprague-Dawley rats were excised and exposed to an I/R protocol (1 h of ischemia, followed by 2 h of reperfusion) on a modified Langendorff apparatus. Hearts from female rats showed significantly smaller infarct sizes than hearts from males (23 ± 4 vs. 40 ± 5% of the zone at risk, respectively; P < 0.05). Administration of HMR-1098, a sarcolemmal KATP channel blocker, abolished the sex difference in infarct size (42 ± 4 vs. 45 ± 5% of the zone at risk in hearts from female and male rats, respectively; P = not significant). Further experiments showed that blocking the KATP channels in ischemia, and not reperfusion, was sufficient to increase infarct size in female rats. These data demonstrate that sarcolemmal KATP channels are centrally involved in mechanisms that underlie sex differences in the susceptibility of the intact heart to I/R injury.

scholarly journals Inhibiting miR-205 Alleviates Cardiac Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Function, and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Yuerong Xu ◽  
Wangang Guo ◽  
Di Zeng ◽  
Yexian Fang ◽  
Runze Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Infarct Size ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Cardiac Ischemia ◽  
Myocardial Infarct Size ◽  
Neonatal Cardiomyocytes

Background. miR-205 is important for oxidative stress, mitochondrial dysfunction, and apoptosis. The roles of miR-205 in cardiac ischemia/reperfusion (I/R) injury remain unknown. The aim of this research is to reveal whether miR-205 could regulate cardiac I/R injury by focusing upon the oxidative stress, mitochondrial function, and apoptosis. Methods. Levels of miR-205 and Rnd3 were examined in the hearts with I/R injury. Myocardial infarct size, cardiac function, oxidative stress, mitochondria function, and cardiomyocyte apoptosis were detected in mice with myocardial ischemia/reperfusion (MI/R) injury. The primary neonatal cardiomyocytes underwent hypoxia/reoxygenation (H/R) to simulate MI/R injury. Results. miR-205 levels were significantly elevated in cardiac tissues from I/R in comparison with those from Sham. In comparison with controls, levels of Rnd3 were significantly decreased in the hearts from mice with MI/R injury. Furthermore, inhibiting miR-205 alleviated MI/R-induced apoptosis, reduced infarct size, prevented oxidative stress increase and mitochondrial fragmentation, and improved mitochondrial functional capacity and cardiac function. Consistently, overexpression of miR-205 increased infarct size and promoted apoptosis, oxidative stress, and mitochondrial dysfunction in mice with MI/R injury. In cultured mouse neonatal cardiomyocytes, downregulation of miR-205 reduced oxidative stress in H/R-treated cardiomyocytes. Finally, inhibiting Rnd3 ablated the cardioprotective effects of miR-205 inhibitor in MI/R injury. Conclusions. We conclude that inhibiting miR-205 reduces infarct size, improves cardiac function, and suppresses oxidative stress, mitochondrial dysfunction, and apoptosis by promoting Rnd3 in MI/R injury. miR-205 inhibitor-induced Rnd3 activation is a valid target to treat MI/R injury.

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