scholarly journals Hydroxytyrosol Protects against Myocardial Ischemia/Reperfusion Injury through a PI3K/Akt-Dependent Mechanism

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-hao Pei ◽  
Jiao Chen ◽  
Liang Xie ◽  
Xiao-min Cai ◽  
Run-Hua Yang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Systolic Function ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Mechanistic Study ◽  
Myocardial Infarct Size ◽  
Myocardial Apoptosis ◽  
Group I ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Objective. To investigate the effects and mechanisms of hydroxytyrosol (HT) during the pathogenesis of myocardial ischemia reperfusion (I/R) in rat hearts.Methods. The rats were randomized into five groups: sham group, I/R group, HT+I/R group, HT+LY294002+I/R group, and LY+I/R group. Myocardial infarct size, markers of oxidative stress, extent of myocardial apoptosis, echocardiographically assessed cardiac function, and expression of Akt and GSK 3βwere measured in each group.Results. Prereperfusion administration of HT was associated with a significantly smaller area of myocardial infarction and remarkably decreased level of myocardial apoptosis and necrosis, as evidenced by a lower apoptotic index, reduced cleaved caspase-3, and the serum activities of lactate dehydrogenase and creatinine kinase MB. Moreover, HT also attenuated the impairment of cardiac systolic function. However, cotreatment with LY294002 and HT completely abolished the above cardioprotective effects of HT. A subsequent mechanistic study revealed that the cardioprotective effects of HT during the process of I/R of the myocardium were dependent on the activation of the Akt/GSK3βpathway.Conclusion. Pretreatment with HT may have antiapoptotic and cardioprotective effects against myocardial I/R injury, and these effects seem to be related to the activation of the Akt/GSK3βpathway in the myocardium.

scholarly journals Troxerutin Preconditioning Modulates the Activity of TLR4/NF-κB Signaling Pathway and Mitochondrial ATP-Sensitive Potassium Channels in a Rat Model of Myocardial Ischemia/Reperfusion Injury

2021 ◽  
Author(s):  
Farid Masoud ◽  
Behnaz Mokhtari ◽  
Sanaz Gholami ◽  
Aniseh Javadi ◽  
Reza Badalzadeh
Keyword(s):  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Heart Diseases ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Ldh Release ◽  
Myocardial Ischemia Reperfusion

Abstract Purpose Given the rising prevalence of ischemic heart diseases (IHD), investigations for achieving effective treatments are required. The purpose of this study is further understanding of troxerutin's impact on inflammatory response induced by myocardial ischemia/reperfusion (MI/R) injury, and the role of toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) signaling pathway and mitochondrial ATP-sensitive potassium (mitoKATP) channels in this scenario. Methods Sixty male Wistar rats were randomly divided into six groups: Control, troxerutin-receiving, MI/R, MI/R plus troxerutin, MI/R plus 5-hydroxydecanoate (5-HD), and MI/R plus troxerutin and 5-HD. The Langendorff-perfused hearts of animals were subjected to 30 min of left anterior descending coronary artery (LAD) ligation and 45 min of reperfusion. Troxerutin (150 mg/kg/day) was administered for 4 weeks prior to MI/R. 5-HD (100 µM) was added to the perfusion solution 20 min before the ischemia. Myocardial infarct size (IS), lactate dehydrogenase (LDH) release, the expressions of TLR4 and NF-κB, and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were measured. Results Troxerutin preconditioning significantly reduced IS (P < 0.05) and LDH release (P < 0.05). Pretreatment with troxerutin decreased the expressions of TLR4 (P < 0.05) and NF-κB (P < 0.01), and reduced the levels of TNF-α (P < 0.01) and IL-1β (P < 0.05). Inhibition of mitoKATP channels by 5-HD significantly reversed the cardioprotective effects of troxerutin (P < 0.05). Conclusion The present work revealed that troxerutin preconditioning has cardioprotective effects against MI/R damage, which are partly mediated through anti-inflammatory effects and the activation of mitoKATP channels.

scholarly journals Ophiopogonin D Reduces Myocardial Ischemia-Reperfusion Injury via Upregulating CYP2J3/EETs in Rats

2018 ◽  
Vol 49 (4) ◽  
pp. 1646-1658 ◽  
Author(s):  
Xiaoyan Huang ◽  
Yuguang Wang ◽  
Yi Wang ◽  
Liang Yang ◽  
Jia Wang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Apoptotic Effects

Background/Aims: Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase (CYP) metabolites of arachidonic acid and have multiple cardiovascular effects. Ophiopogonin D (OP-D) is an important effective monomeric component in Shenmai injection (SM-I). Both have been reported to have a variety of biological functions, including anti-inflammatory, anti-oxidant, and anti-apoptotic effects. We previously demonstrated that OP-D–mediated cardioprotection involves activation of CYP2J2/3 and enhancement of circulating EETs levels in vitro and can be developed as a novel drug for the therapy of myocardial ischemia-reperfusion (MI/R) injury. We therefore hypothesized that the protective effects of OP-D and SM-I against MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in vivo. Methods: A rat model of MI/R injury was generated by ligation of the left anterior descending coronary artery for 40 min, followed by reperfusion for 2 h to determine the protective effects and potential mechanisms of OP-D and SM-I. Electrocardiogram and ultrasonic cardiogram were used to evaluate cardiac function; 2,3,5-triphenyltetrazolium chloride was used to measure myocardial infarct size; hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of myocardial tissue; and the expression of related proteins in the mechanistic study was observed by western blot analysis. Results: We found that OP-D and SM-I exert protective effects on MI/R injury, including regulation of cardiac function, reduction of lactate dehydrogenase and creatine kinase production, attenuation of myocardial infarct size, and improvement of the recovery of damaged myocardial structures. We found that OP-D and SM-I activate CYP2J3 expression and increase levels of circulating 11,12-EET in MI/R-injured rats. Conclusion: We tested the hypothesis that the cardioprotective effects of OP-D and SM-I on MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in rats. Taken together, our results show that the effects of OP-D and SM-I were also mediated by the activation of the PI3K/Akt/eNOS signaling pathway, while inhibition of the NF-κB signaling pathway and antioxidant and anti-apoptotic effects were involved in the cardioprotective effects of OP-D and SM-I.

scholarly journals Cardioprotective Effects of Genistin in Rat Myocardial Ischemia-Reperfusion Injury Studies by Regulation of P2X7/NF-κB Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Meng Gu ◽  
Ai-bin Zheng ◽  
Jing Jin ◽  
Yue Cui ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Mitochondrial Morphology ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

The present study aimed to assess the effects and mechanisms of genistin in the rat model of myocardial ischemia reperfusion injury. The rat hearts were exposed to the left anterior descending coronary artery (LAD) ligation for 30 min followed by 1 h of reperfusion. In the rat of myocardial ischemia/reperfusion (MI/R), it was found that genistin pretreatment reduced myocardial infarct size, improved the heart rate, and decreased creatine kinase (CK) and lactate dehydrogenase (LDH) levels in coronary flow. This pretreatment also increased catalase (CAT), superoxide dismutase (SOD) activities but decreased glutathione (GSH), malondialdehyde (MDA) levels. Furthermore, we determined that genistin can ameliorate the impaired mitochondrial morphology and oxidation system; interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-α(TNF-α) levels were also recovered. Besides, related-proteins of nuclear factor kappa-B (NF-κB) signal pathway activated by P2X7 were investigated to determine the molecular mechanism of genistin and their expressions were measured by western blot. These results presented here demonstrated that genistin enhanced the protective effect on the rats with myocardial ischemia reperfusion injury. Therefore, the cardioprotective effects of genistin may rely on its antioxidant and anti-inflammatory activities via suppression of P2X7/NF-κB pathways.

scholarly journals The Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of the Bauhinia Championii Flavone are Connected with Protection Against Myocardial Ischemia/Reperfusion Injury

2016 ◽  
Vol 38 (4) ◽  
pp. 1365-1375 ◽  
Author(s):  
Jie Jian ◽  
Feifei Xuan ◽  
Feizhang Qin ◽  
Renbin Huang
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Previous studies have demonstrated that Bauhinia championii flavone (BCF) exhibits anti-oxidative, anti-hypoxic and anti-stress properties. This study was designed to investigate whether BCF has a cardioprotective effect against myocardial ischemia/reperfusion (I/R) injuries in rats and to shed light on its possible mechanism. Methods: The model of I/R was established by ligating the left anterior descending coronary artery for 30 min, then reperfusing for 180 min. Hemodynamic changes were continuously monitored. The content of malondialdehyde (MDA) as well as the lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. The release of interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis of cardiomyocytes was determined by caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of TLR4, NF-κBp65, Bcl-2 and Bax were detected by western blotting. Results: Pretreatment with BCF significantly reduced the serum levels of LDH, MDA and IL-6, but increased the activities of SOD and GSH-Px. It also attenuated myocardial infarct size, reduced the apoptosis rate and preserved cardiac function. Furthermore, BCF inhibited caspase-3 activity and the expression of TLR4, phosphorylated NF-κBp65 and Bax, but enhanced the expression of Bcl-2. Conclusion: These results provide substantial evidence that BCF exerts a protective effect on myocardial I/R injury, which may be attributed to attenuating lipid peroxidation, the inflammatory response and apoptosis.

Abstract 16381: Novel Thiol-activated H2S Donors Attenuate Myocardial Ischemia/Reperfusion Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Chelsea Organ ◽  
Zhen Li ◽  
Yu Zhao ◽  
Chuntao Yang ◽  
Shashi Bhushan ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Sustained Release ◽  
Murine Model ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background: Hydrogen sulfide (H2S) protects against acute myocardial ischemia/reperfusion (MI/R) injury and heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. One of the major limitations of currently available H2S donors is poor pharmacokinetics profiles that result in very rapid and uncontrolled H2S release. NSHD-1 and NSHD-2 are recently developed thiol-activated H2S donors designed for sustained release of H2S upon activation by molecules containing thiol groups such as cysteine and glutathione. We hypothesized that these novel H2S donors would generate H2S for extended periods and ameliorate myocardial cell death following MI/R in an in vivo murine model. Methods and Results: C57BL6/J male mice (10-12 weeks of age) were subjected to 45 minutes of MI followed by 24 hours of R. At the time of reperfusion, animals received Vehicle (0.5% THF), NSHD-1 (50 μg/kg and 100 μg/kg), or NSHD-2 (50 μg/kg) by direct intracardiac (i.c.) injection. In addition, at 4 hours of R, plasma was collected for troponin-I measurements. In preliminary studies we observed sustained release of H2S with both of these H2S donors. Myocardial infarct size was reduced by 35% (p < 0.01 vs. Vehicle) in mice treated with NSHD-1 (100 μg/kg), 43% (p < 0.05 vs. Vehicle) in mice treated with NSHD-2 (50 μg/kg), and 54% (p < 0.01 vs. Vehicle) in mice treated with NSHD-2 (100 μg/kg). Conclusions: NSHD-1 and NSHD-2 significantly attenuate MI/R injury in a murine model. Experiments are currently underway to further define the in vivo pharmacokinetics of H2S release from these agents, mechanisms of action, and safety profile.

scholarly journals Daucosterol pretreatment ameliorates myocardial ischemia reperfusion injury via ROS-mediated NLRP3 inflammasome activation

2020 ◽  
Vol 19 (5) ◽  
pp. 1031-1036
Author(s):  
Guixiang Zhao ◽  
Xiaoyun Ma ◽  
Juledezi Hailati ◽  
Zhen Bao ◽  
Maerjiaen Bakeyi ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Inflammasome Activation ◽  
Myocardial Infarct Size ◽  
Nlrp3 Inflammasome Activation ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Purpose: To determine the involvement of NLRP3 signaling pathway in the preventive role of daucosterol in acute myocardial infarction (AMI).Methods: H9C2 cells were pretreated with daucosterol before hypoxia/reoxygenation (HR) injury. Myocardial ischemia reperfusion (IR) was established in male SD rats, followed by reperfusion. Myocardial infarct size was measured. The serum levels of creatine kinase (CK), lactate  dehydrogenase (LDH), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were determined using commercial kits. NLRP3 inflammasome activation was assessed by western blotting.Results: Myocardial infarct size was smaller after IR injury in rats pretreated with daucosterol (10 and 50 mg/kg) than that pretreated with daucosterol (0 and 1 mg/kg). The increase in LDH, CK, and MDA levels after IR injury was reduced following daucosterol pretreatment. Reactive oxygen species (ROS) production increased, whereas T-SOD activity decreased after IR injury. These changes were prevented by pretreatment of daucosterol (10 and 50 mg/kg). Protein expression of NLRP3 inflammasome increased after IR injury in H9C2 cells while pretreatment with daucosterol inhibited the upregulation of NLRP3 inflammasome.Conclusion: The cardioprotective effect of daucosterol pretreatment appears to be mediated via the inactivation of ROS-related NLRP3 inflammasome, suggesting that daucosteol might be a potential therapeutic drug for AMI. Keywords: Daucosterol, Myocardial ischemia, Reperfusion injury, Reactive oxygen species, NLRP3 inflammasome

Coronary endothelial P-selectin in pathogenesis of myocardial ischemia-reperfusion injury

1998 ◽  
Vol 275 (5) ◽  
pp. H1865-H1872 ◽  
Author(s):  
Anthony J. Palazzo ◽  
Steven P. Jones ◽  
Donald C. Anderson ◽  
D. Neil Granger ◽  
David J. Lefer
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Wild Type ◽  
Area At Risk ◽  
Myocardial Ischemia Reperfusion

We investigated in vivo coronary P-selectin expression and its pathophysiological consequences in a murine model of myocardial ischemia-reperfusion (MI/R) using wild-type and P-selectin deficient (−/−) mice. Coronary P-selectin expression [μg monoclonal antibody (MAb)/g tissue] was measured using a radiolabeled MAb method after 30 min of myocardial ischemia and 20 min of reperfusion. P-selectin expression in wild-type mice was significantly ( P< 0.01) elevated in the ischemic zone (0.070 ± 0.010) compared with the nonischemic zone (0.037 ± 0.008). Myocardial P-selectin expression was nearly undetectable in P-selectin −/− mice after MI/R. Furthermore, myocardial infarct size (% of area at risk) after 30 min of myocardial ischemia and 120 min of reperfusion was 42.5 ± 4.4 in wild-type mice and 24.4 ± 4.0 in P-selectin −/− mice ( P < 0.05). In additional experiments of prolonged myocardial ischemia (60 min) and reperfusion (120 min), myocardial infarct size was similar in P-selectin −/− mice and wild-type mice. Our results clearly demonstrate the involvement of coronary P-selectin in the development of myocardial infarction after MI/R.

scholarly journals Schisandrol A Attenuates Myocardial Ischemia/Reperfusion-Induced Myocardial Apoptosis through Upregulation of 14-3-3θ

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Shuaishuai Gong ◽  
Jincheng Liu ◽  
Shiyao Wan ◽  
Weiwei Yang ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Functional Protein ◽  
Myocardial Apoptosis ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms ◽  
Stress Damage

Schisandrol A (SA), one of the most abundant bioactive lignans extracted from the Schisandra chinensis (Turcz.) Baill., has multiple pharmacological properties. However, the underlying mechanisms of SA in protection against myocardial ischemia/reperfusion (MI/R) injury remain obscure. The present experiment was performed to explore the cardioprotective effects of SA in MI/R injury and hypoxia/reoxygenation- (H/R-) induced cardiomyocyte injury and clarify the potential underlying mechanisms. SA treatment significantly improved MI/R injury as reflected by reduced myocardium infarct size, attenuated histological features, and ameliorated biochemical indicators. In the meantime, SA could profoundly ameliorate oxidative stress damage as evidenced by the higher glutathione peroxidase (GSH-Px) as well as lower malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, SA alleviated myocardial apoptosis as evidenced by a striking reduction of cleaved caspase-3 expression and increase of Bcl-2/Bax ratio. Further experiments demonstrated that SA had certain binding capability to the key functional protein 14-3-3θ. Mechanistically, SA prevented myocardial apoptosis through upregulating 14-3-3θ expression. Interestingly, siRNA against 14-3-3θ could promote apoptosis of cardiomyocytes, and H/R injury after knockdown of 14-3-3θ could further aggravate apoptosis, while overexpression of 14-3-3θ could significantly reduce apoptosis induced by H/R injury. Further, 14-3-3θ siRNA markedly weakened the antiapoptotic role of SA. Our results demonstrated that SA could exert apparent cardioprotection against MI/R injury and H/R injury, and potential mechanisms might be associated with inhibition of cardiomyocyte apoptosis at least partially through upregulation of 14-3-3θ.

scholarly journals Pre-clinical Evidence: Berberine as a Promising Cardioprotective Candidate for Myocardial Ischemia/Reperfusion Injury, a Systematic Review, and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Cong Chen ◽  
Qian Lin ◽  
Xue-Ying Zhu ◽  
Junyan Xia ◽  
Tianshi Mao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Myocardial Ischemia ◽  
Clinical Evidence ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Control Groups ◽  
Myocardial Ischemia Reperfusion

Objective: Myocardial ischemia/reperfusion (I/R) injury is one of the causes of most cardiomyocyte injuries and deaths. Berberine (BBR) has been suggested a potential to exert protective effects against myocardial I/R injury. This systematic review aims to determine the intrinsic mechanisms of BBR's protective effects in myocardial I/R injury.Methods: Seven databases were searched for studies performed from inception to July 2020. Methodological quality was assessed by SYRCLE's-RoB tool.Results: Ten studies including a total of 270 animals were included in this study. The methodology quality scores of the included studies ranged from 5 to 7 points. The meta-analysis we conducted demonstrated that BBR significantly reduced myocardial infarct size and the incidence of ventricular arrhythmia, compared to control groups (P &lt; 0.00001). Cardiac function of animals in the BBR treatment group was also markedly increased (P &lt; 0.00001). The index of myocardial apoptosis and the levels of biomarkers of myocardial infarction (LDH and CK) were also decreased in the BBR treatment groups compared to the control groups (P &lt; 0.00001).Conclusions: The pre-clinical evidence, according to our study, showed that BBR is a promising therapeutic agent for myocardial I/R injury. However, this conclusion should be further investigated in clinical studies.

Sign in / Sign up

Export Citation Format

Share Document