Protective effects of α-bisabolol on altered hemodynamics, lipid peroxidation, and nonenzymatic antioxidants in isoproterenol-induced myocardial infarction: In vivo and in vitro evidences

2018 ◽  
Vol 32 (10) ◽  
pp. e22200 ◽  
Author(s):  
Mohamed Fizur Nagoor Meeran ◽  
Farah Laham ◽  
Hasan Al-Taee ◽  
Sheikh Azimullah ◽  
Shreesh Ojha
Keyword(s):  
Myocardial Infarction ◽  
Lipid Peroxidation ◽  
Protective Effects ◽  
Nonenzymatic Antioxidants

scholarly journals Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2

2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Yi Peng ◽  
Ji-Ling Zhao ◽  
Zhi-Yong Peng ◽  
Wei-Fang Xu ◽  
Guo-Long Yu
Keyword(s):  
Myocardial Infarction ◽  
Inflammatory Responses ◽  
Luciferase Assay ◽  
Protective Effects ◽  
Functional Studies ◽  
Protein Levels ◽  
Cardioprotective Effects ◽  
Apoptotic Proteins

Abstract Mesenchymal stem cell (MSC) therapy is a promising approach against myocardial infarction (MI). Studies have demonstrated that MSCs can communicate with other cells by secreting exosomes. In the present study, we aimed to identify exosomal microRNAs that might contribute to MSC-mediated cardioprotective effects. Primary cardiomyocytes were deprived of oxygen and glucose to mimic MI in vitro. For the animal model of MI, the left anterior descending artery was ligated for 1 h, followed by reperfusion for 12 h. MSC-derived exosomes were used to treat primary cardiomyocytes or mice. Cardioprotection-related microRNAs were determined, followed by target gene identification and functional studies with quantitative PCR, western blotting, MTT assay, flow cytometry assay, chromatin immunoprecipitation and dual-luciferase assay. We found that MSC co-culture reduced OGD-induced cardiomyocyte apoptosis and inflammatory responses. Cardioprotection was also observed upon treatment with MSC-derived exosomes in vitro and in vivo. In line with this, exosome uptake led to a significant increase in miR-25-3p in cardiomyocytes. Depletion of miR-25-3p in MSCs abolished the protective effects of exosomes. Mechanistically, miR-25-3p directly targeted the pro-apoptotic genes FASL and PTEN and reduced their protein levels. Moreover, miR-25-3p decreased the levels of EZH2 and H3K27me3, leading to derepression of the cardioprotective gene eNOS as well as the anti-inflammatory gene SOCS3. Inhibition of EZH2 or overexpression of miR-25-3p in cardiomyocytes was sufficient to confer cardioprotective effects in vitro and in vivo. We concluded that exosomal miR-25-3p from MSCs alleviated MI by targeting pro-apoptotic proteins and EZH2.

scholarly journals Cannabinoid receptor 2 deletion deteriorates myocardial infarction through the down-regulation of AMPK-mTOR-p70S6K signaling-mediated autophagy

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Yao Hu ◽  
Yu Tao ◽  
Jing Hu
Keyword(s):  
Myocardial Infarction ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Cannabinoid Receptor ◽  
Cell Counting ◽  
Protective Effects ◽  
Cannabinoid Receptor 2 ◽  
Related Proteins

AbstractCannabinoid receptor 2 (CB2R) has been reported to play an important role in the regulation of pathogenesis and progression of myocardial infarction (MI). Here we tried to investigate its potential mechanisms. The ratio of infarct size in heart issue was detected by TTC staining, and cardiac functions were calculated according to echocardiographic evaluation. Cell viability in cardiomyocytes was investigated by Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Western blot was used to detect autophagy-related proteins including Beclin-1, LC3, p62, adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target of rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K) signaling-related proteins including AMPK, mTOR, p70S6K, and their phosphorylation formation. Rapamycin was used for the induction of autophagy. Cleaved caspase-3 and Bax were detected for analyzing apoptosis. TEM was used for the detection of autophagosomes. We found that CB2R deletion (CB2R KO) largely deteriorated the severity of MI and the cardiac function as well as cell viability of cardiomyocytes. Knocking out CB2R decreased the level of autophagy in heart issues from MI mice as well as cardiomyocytes under oxygen-glucose deprivation (OGD). Furthermore, CB2R dysfunction significantly attenuated the cardiac protective effects of rapamycin both in vivo and in vitro. Finally, we found that CB2R-mediated autophagy was induced by AMPK-mTOR-p70S6K signaling pathway. Our current study demonstrated for the first time that CB2R deletion led to a detrimental effect of MI through the dysfunction of AMPK-mTOR-p70S6K signaling pathway, which might provide a novel insight in the treatment of MI.

scholarly journals Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Zheng Yang ◽  
Qing-Qing Wu ◽  
Yang Xiao ◽  
Ming Xia Duan ◽  
Chen Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Coronary Artery Ligation ◽  
No Production ◽  
Protective Effects ◽  
Artery Ligation ◽  
Nos Inhibitors

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.

scholarly journals The influence of mannitol on myoglobinuric acute renal failure: functional, biochemical, and morphological assessments.

1991 ◽  
Vol 2 (4) ◽  
pp. 848-855
Author(s):  
R A Zager ◽  
C Foerder ◽  
C Bredl
Keyword(s):  
Lipid Peroxidation ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Membrane Vesicles ◽  
Tubular Cell ◽  
Protective Effects ◽  
Beneficial Action ◽  
Cellular Energetics

This study was undertaken to explore the protective influence of mannitol against the glycerol model of myohemoglobinuric acute renal failure. Three hypotheses were tested: (1) mannitol confers cytoprotection by acutely blunting renal hypoperfusion, thereby improving tubular cell energetics; (2) as an hydroxyl radical (OH.) scavenger, mannitol mitigates Fe-driven lipid peroxidation and, hence, decreases tubular cell necrosis; and (3) mannitol prevents intrarenal heme pigment trapping, decreasing cast formation. Rats were injected with 50% glycerol (10 mL/kg im), followed immediately by an iv mannitol (1.25 mL/100 g over 1 h) or sham infusion. Mannitol induced a brisk diuresis (approximately 5.7 mL/2 h; approximately 35 mg of heme protein excreted), whereas glycerol controls were anuric. Mannitol did not significantly increase postglycerol RBF (2.8 mL/min), and it paradoxically worsened cellular energetics, halving cortical ATP concentrations at 1 h. However, this adverse effect on ATP was transient, correlating with active diuresis. Glycerol did not induce convincing in vivo lipid peroxidation (malondialdehyde; conjugated diene assay), and mannitol did not block Fe-driven in vitro lipid peroxidation of isolated brush border membrane vesicles. Na benzoate, an OH. scavenger, conferred no in vivo or in vitro protection. However, Na2SO4, not an OH. scavenger, reproduced the diuretic and in vivo protective effects of mannitol. Purified myoglobin infusion (35 mg) largely negated the beneficial action of mannitol. It was concluded that mannitol confers functional but not cytoprotection against the glycerol acute renal failure model, it acutely worsens renal bioenergetics, and its protective influence is probably due to a diuretic, not an antioxidant, effect.

scholarly journals Oxidoreductases generate hydrogen peroxide that drives iron-dependent lipid peroxidation during ferroptosis

2020 ◽  
Author(s):  
Bo Yan ◽  
Youwei Ai ◽  
Ze Zhang ◽  
Qi Sun ◽  
Yan Ma ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Cytochrome B5 ◽  
Antioxidant Systems ◽  
Protective Effects ◽  
Genetic Ablation ◽  
Nadh Cytochrome ◽  
Cell Commitment

SUMMARYThe inhibition of antioxidant systems of glutathione peroxidase 4 (GPX4) or ferroptosis suppressor protein 1 (FSP1) causes iron-dependent peroxidation of polyunsaturated phospholipids that leads to cell death, a process known as ferroptosis. The mechanisms underlying iron-dependent lipid peroxidation are under active debate. Here, we report that two endoplasmic reticulum-residing oxidoreductases, NADPH-cytochrome P450 reductase (POR) and NADH-cytochrome b5 reductase (CYB5R1), are responsible for the iron-dependent peroxidation of polyunsaturated phospholipids and membrane disruption that executes ferroptosis. Genetic ablation of POR and CYB5R1 or mutations that eliminate POR’s electron transfer activity blocked ferroptosis. In vitro enzymatic assays established that POR and CYB5R1 catalyze hydrogen peroxide production by transferring electrons from NADPH/NADH to oxygen, which is then used to carry out iron-dependent lipid peroxidation via a Fenton reaction. The lipid peroxidation reaction catalyzed by POR and CYB5R1 additively disrupts polyunsaturated phospholipid-containing liposomes. Finally, POR knockdown confers significant protective effects during concanavalin A-induced, ferroptosis-associated acute liver injury in vivo. Our study thus indicates that POR and CYB5R1 are the enzymes of the “oxidant” system that operates to contravene the antioxidant GPX4/FSP1 systems; the balance between these two systems determines cell commitment to ferroptosis.

scholarly journals Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signaling pathway

2021 ◽  
Author(s):  
Jianqiang HU ◽  
Wenjing Gu ◽  
Ning Ma ◽  
Xiaoye Fan ◽  
Xinxin Ci
Keyword(s):  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Lipid Peroxide ◽  
Kidney Injury ◽  
Iron Accumulation ◽  
Protective Effects ◽  
Nrf2 Signaling Pathway

Background and purpose: Increasing evidence suggests that ferroptosis plays a key role in the pathophysiology of acute kidney injury induced by cisplatin. The Nrf2 signaling pathway regulates oxidative stress and lipid peroxidation and positively regulates cisplatin-induced AKI (CI-AKI). However, Nrf2 and its activator leonurine on ferroptosis after CI-AKI remain unclear. Experimental Approach: The anti-ferroptotic effects of Nrf2 and its activator leonurine were assessed using a mouse model of cisplatin-induced AKI. In vitro, the potential effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined. Key Results: As expected, Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, further aggravating CI-AKI. The Nrf2 activator leonurine prevented iron accumulation and lipid peroxidation and inhibited ferroptosis in vitro, while these effects were abolished in siNrf2-treated cells. Moreover, leonurine potently ameliorated cisplatin-induced renal damage, as indicated by the assessment of SCr, BUN, KIM-1, and NGAL. Importantly, leonurine activated the Nrf2 antioxidative signaling pathway and prohibited changes in ferroptosis-related morphological and biochemical indicators, such as the MDA level, SOD and GSH depletion and GPX4 and xCT downregulation, in CI-AKI. Moreover, Nrf2 KO mice were more susceptible to ferroptosis after CI-AKI than control mice, and the protective effects of leonurine on AKI and ferroptosis were largely abolished in Nrf2 KO mice. Conclusion and Implications: These data suggest that the renal protective effects of Nrf2 and its activator leonurine on CI-AKI are achieved at least partially by inhibiting lipid peroxide-mediated ferroptosis and highlight the potential of leonurine as a CI-AKI treatment.

Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

1976 ◽  
Vol 35 (01) ◽  
pp. 049-056 ◽  
Author(s):  
Christian R Klimt ◽  
P. H Doub ◽  
Nancy H Doub
Keyword(s):  
Myocardial Infarction ◽  
Secondary Prevention ◽  
Case Control ◽  
Therapeutic Effects ◽  
Case Control Studies ◽  
Definitive Answer ◽  
Inhibition Of Platelet Aggregation ◽  
Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

Antioxidant Activity, Phenolic Content and Hematoprotective Effects of Cleome arabica Polyphenolic Leaf Extract

2019 ◽  
Author(s):  
C. Tigrine ◽  
A. Kameli
Keyword(s):  
Antioxidant Activity ◽  
Biological Effects ◽  
Reducing Power ◽  
Hematological Toxicity ◽  
Protective Effects ◽  
Ferrous Ions ◽  
Polyphenolic Extract ◽  
Cleome Arabica

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

Sign in / Sign up

Export Citation Format

Share Document