Neohesperidin alleviated pathological damage and immunological imbalance in rat myocardial ischemia-reperfusion injury via inactivation of JNK and NF-κB p65

2021 ◽  
Vol 85 (2) ◽  
pp. 251-261
Author(s):  
Aihua Li ◽  
Xin Zhang ◽  
Qiuping Luo
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Oxidative Stress Markers ◽  
Antitumor Effects ◽  
Stress Markers ◽  
Myocardial Ischemia Reperfusion

ABSTRACT Neohesperidin (NEO) exerts antiviral, antioxidant, anti-inflammation, and antitumor effects in some diseases. The purpose of this study was to investigate the effect and mechanism of NEO on myocardial ischemia-reperfusion (I/R) injury. Results indicated that NEO suppressed the levels of serum inflammatory cytokines, myocardial damage markers, and oxidative stress markers, and increased the levels of antioxidant in myocardial I/R rats. NEO also inhibited cell apoptosis. Besides, NEO also inhibited the phosphorylation of c-Jun N-terminal kinases (JNK) and nuclear factor kappa B (NF-κB) p65. Furthermore, the protective effects of NEO on myocardial tissue damage, inflammatory cytokines, myocardial injury markers, oxidative stress markers, cell apoptosis, spleen, thymus and liver indices, and phagocytic indices were reversed by JNK activator and NF-κB activator, respectively. In conclusion, NEO alleviates myocardial damage, oxidative stress, cell apoptosis, and immunological imbalance in I/R injury via the inactivation of JNK and NF-κB, making NEO a potential agent for myocardial I/R therapy.

scholarly journals Combined Therapy with SS31 and Mitochondria Mitigates Myocardial Ischemia-Reperfusion Injury in Rats

2018 ◽  
Vol 19 (9) ◽  
pp. 2782 ◽  
Author(s):  
Fan-Yen Lee ◽  
Pei-Lin Shao ◽  
Christopher Wallace ◽  
Sarah Chua ◽  
Pei-Hsun Sung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Adult Male ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Left Ventricular Ejection ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Myocardial Ischemia Reperfusion ◽  
Sirt3 Expression

Myocardial ischemia-reperfusion (IR) injury contributes to adverse cardiac outcomes after myocardial ischemia, cardiac surgery, or circulatory arrest. In this study, we evaluated the ability of combined SS31-mitochondria (Mito) therapy to protect heart cells from myocardial IR injury. Adult male SD rats (n = 8/each group) were randomized: group 1 (sham-operated control), group 2 (IR, 30-min ischemia/72 h reperfusion), group 3 (IR-SS31 (2 mg intra-peritoneal injection at 30 min/24 h/48 h after IR)), group 4 (IR-mitochondria (2 mg/derived from donor liver/intra-venous administration/30 min after IR procedure)), and group 5 (IR-SS31-mitochondria). In H9C2 cells, SS31 suppressed menadione-induced oxidative-stress markers (NOX-1, NOX-2, oxidized protein) while it increased SIRT1/SIRT3 expression and ATP levels. In adult male rats 72 h after IR, left ventricular ejection fraction (LVEF) was highest in sham-operated control animals and lowest in the IR group. LVEF was also higher in IR rats treated with SS31-Mito than untreated IR rats or those treated with Mito or SS31 alone. Areas of fibrosis/collagen-deposition showed the opposite pattern. Likewise, levels of oxidative-stress markers (NOX-1, NOX-2, oxidized protein), inflammatory markers (MMP-9, CD11, IL-1β, TNF-α), apoptotic markers (mitochondrial-Bax, cleaved-caspase-3, PARP), fibrosis markers (p-Smad3, TGF-β), DNA-damage (γ-H2AX), sarcomere-length, and pressure/volume overload markers (BNP, β-MHC) all showed a pattern opposite that of LVEF. Conversely, anti-apoptotic (BMP-2, Smad1/5) and energy integrity (PGC-1α/mitochondrial cytochrome-C) markers exhibited a pattern identical to that of LVEF. This study demonstrates that the combined SS31-Mito therapy is superior to either therapy alone for protecting myocardium from IR injury and indicates that the responsible mechanisms involved increased SIRT1/SIRT3 expression, which suppresses inflammation and oxidative stress and protects mitochondrial integrity.

scholarly journals Dexmedetomidine Protects against Myocardial Ischemia/Reperfusion Injury by Ameliorating Oxidative Stress and Cell Apoptosis through the Trx1-Dependent Akt Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Zhi-lin Wu ◽  
Jacques Robert Jeppe Davis ◽  
Yi Zhu
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Akt Pathway ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion ◽  
Isolated Rat

Dexmedetomidine (Dex) was reported to reduce oxidative stress and protect against myocardial Ischemia/Reperfusion (I/R) injury. However, the molecular mechanism involved in its antioxidant property is not fully elucidated. The present study was aimed at investigating whether the Trx1/Akt pathway participated in the cardioprotective effect of Dex. In the present study, I/R-induced myocardial injury in isolated rat hearts and OGD/R-induced injury in H9c2 cardiomyocytes were established. Our findings suggested that Dex ameliorated myocardial I/R injury by improving cardiac function, reducing myocardial apoptosis and oxidative stress, which was manifested by increased GSH and SOD contents, decreased ROS level, and MDA generation in both the isolated rat hearts and OGD/R-treated H9C2 cells. More importantly, it was found that the level of Trx1 was preserved, and Akt phosphorylation was significantly upregulated by Dex treatment. However, these effects of Dex were abolished by PX-12 (a specific Trx1 inhibitor) administration. Taken together, this study suggests that Dex plays a protective role in myocardial I/R injury, improves cardiac function, and relieves oxidative stress and cell apoptosis. Furthermore, our results present a novel signaling mechanism that the cardioprotective effect of Dex is at least partly achieved through the Trx1-dependent Akt pathway.

scholarly journals Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Mi Xiang ◽  
Yingdong Lu ◽  
Laiyun Xin ◽  
Jialiang Gao ◽  
Chang Shang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
High Morbidity ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy.

scholarly journals microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

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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