scholarly journals MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Xue Han ◽  
Daili Chen ◽  
Ning Liufu ◽  
Fengtao Ji ◽  
Qingshi Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Cardiomyocyte Apoptosis ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Myocardial Oxidative Stress

Background. The heart is one of the most commonly affected organs during sepsis. Mitsugumin-53 (MG53) has attracted attention in research due to its cardioprotective function. However, the role of MG53 in sepsis-induced myocardial dysfunction (SIMD) remains unknown. The purpose of this study was to explore the underlying mechanism of MG53 in SIMD and investigate its potential relationship with peroxisome proliferator-activated receptor-α (PPARα). Methods. The cecal ligation and puncture (CLP) model was created to induce SIMD in rats. Protein levels of MG53 and PPARα, cardiac function, cardiomyocyte injury, myocardial oxidative stress and inflammatory indicators, and cardiomyocyte apoptosis were measured at 18 h after CLP. The effects of MG53 on PPARα in SIMD were investigated via preconditioning recombinant human MG53 (rhMG53) and PPARα antagonist GW6471. Results. The expression of MG53 and PPARα sharply decreased in the myocardium at 18 h after CLP. Compared with the sham group, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated oxidative stress indicators and proinflammatory cytokines, and excessive cardiomyocyte apoptosis in the CLP group. Supplementation with rhMG53 enhanced myocardial MG53, increased the survival rate with improved cardiac function, and reduced oxidative stress, inflammation, and myocardial apoptosis, which were associated with PPARα upregulation. Pretreatment with GW6471 abolished the abovementioned protective effects induced by MG53. Conclusions. Both MG53 and PPARα were downregulated after sepsis shock. MG53 supplement protects the heart against SIMD by upregulating PPARα expression. Our results provide a new treatment strategy for SIMD.

scholarly journals Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Yan ◽  
Si-Chi Xu ◽  
Chun-Yan Kong ◽  
Xiao-Yang Zhou ◽  
Zhou-Yan Bian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

scholarly journals PPAR-γ Activation Prevents Septic Cardiac Dysfunction via Inhibition of Apoptosis and Necroptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Shiyan Peng ◽  
Junmei Xu ◽  
Wei Ruan ◽  
Suobei Li ◽  
Feng Xiao
Keyword(s):  
Cell Death ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Cardiac Inflammation ◽  
Ppar Γ

Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) γ has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR-γ-mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR-γ by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis. Rats were subjected to cecal ligation and puncture (CLP) with or without PPAR-γ agonist (rosiglitazone) or antagonist T0070907 (T007). After CLP, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated proinflammatory cytokines, and increased apoptosis, necrosis, and necroptosis. This process is corresponded with decreased inhibitor κB (IκBα) and increased NF-κB, receptor-interacting protein kinase-1 (RIP1), RIP3, and mixed lineage kinase-like (MLKL) protein. Activation of PPAR-γ by rosiglitazone pretreatment enhanced PPAR-γ activity and prevented these changes, thereby improving the survival of septic rats. In contrast, inhibition of PPAR-γ by T007 further exacerbated the condition, dropping the survival rate to nearly 0%. In conclusion, PPAR-γ activation by reducing proinflammatory cytokines, apoptosis, and necroptosis in the myocardium prevents septic myocardial dysfunction.

scholarly journals Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Inga Bae-Gartz ◽  
Philipp Kasper ◽  
Nora Großmann ◽  
Saida Breuer ◽  
Ruth Janoschek ◽  
...  
Keyword(s):  
Early Life ◽  
Body Weight Gain ◽  
Hepatic Metabolism ◽  
Underlying Mechanism ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Maternal Exercise

Abstract Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic β-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.

Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation

2014 ◽  
Vol 92 (9) ◽  
pp. 717-724 ◽  
Author(s):  
Ayman M. Mahmoud
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Protective Effect ◽  
Liver Lipid ◽  
Inos Mrna ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intraperitoneal Dose

The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

scholarly journals SIRT3-dependent mitochondrial oxidative stress in sodium fluoride-induced hepatotoxicity and salvage by melatonin

2017 ◽  
Author(s):  
Chao Song ◽  
Jiamin Zhao ◽  
Jingcheng Zhang ◽  
Tingchao Mao ◽  
Beibei Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Binding Activity ◽  
Daily Injection ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor

AbstractOxidative stress induced by fluoride (F) is associated with fluorosis formation, but the underlying molecular mechanism remains unclear. In this study, Melatonin pretreatment suppressed F-induced hepatocyte injury in HepG2 cells. Melatonin increases the activity of superoxide dismutase (SOD2) by enhancing sirtuin 3 (SIRT3)-mediated deacetylation and promotes SOD2 gene expression via SIRT3-regulated DNA-binding activity of forkhead box O3 (FoxO3a), indicating that melatonin markedly enhanced mROS scavenging in F-exposed HepG2 cells. Notably, melatonin activated the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α). PGC-1α interacted with the estrogen-related receptor alpha (ERRα) bound to the SIRT3 promoter, where it functions as a transcription factor to regulate SIRT3 expression. Furthermore, daily injection of melatonin for 30 days inhibited F-induced oxidative stress in mice liver, leading to improvement of liver function. Mechanistic study revealed that the protective effects of melatonin were associated with down-regulation of JNK1/2 phosphorylation in vitro and in vivo. Collectively, our data suggest a novel role of melatonin in preventing F-induced oxidative stress through activation of the SIRT3 pathway.

scholarly journals Sodium–glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in rats after cardiac arrest

2021 ◽  
Author(s):  
Yunke Tan ◽  
Kai Yu ◽  
Lian Liang ◽  
Yuanshan Liu ◽  
Fengqing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Cardiac Function ◽  
Structural Integrity ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Mitochondrial Activity ◽  
Myocardial Oxidative Stress ◽  
Sglt2 Inhibition

Abstract Background: Sodium–glucose co-transporter 2 (SGLT2) inhibition reduces hyperglycaemia and has beneficial effects in heart failure. However, the effect of SGLT2 inhibition with empagliflozin on acute myocardial dysfunction after cardiac arrest (CA) remains unknown.Methods: Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 minutes after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. Results: Empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial contraction band necrosis, myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as myocardial expression of the 𝛽-hydroxy butyrate dehydrogenase 1. Together these metabolic changes were associated with an increase in cardiac ATP production.Conclusions: Empagliflozin favorably affects cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might be of benefit in patients with acute myocardial dysfunction after CA.

scholarly journals Activating the PGC-1α/TERT Pathway by Catalpol Ameliorates Atherosclerosis via Modulating ROS Production, DNA Damage, and Telomere Function: Implications on Mitochondria and Telomere Link

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Yukun Zhang ◽  
Changyuan Wang ◽  
Yue Jin ◽  
Qining Yang ◽  
Qiang Meng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Rehmannia Glutinosa ◽  
Iridoid Glucoside ◽  
Telomere Shortening ◽  
Peroxisome Proliferator Activated Receptor ◽  
Telomere Function ◽  
Luciferase Activity Assay

Catalpol, an iridoid glucoside, has been found present in large quantities in the root of Rehmannia glutinosa L. and showed a strong antioxidant capacity in the previous study. In the present work, the protective effect of catalpol against AS via inhibiting oxidative stress, DNA damage, and telomere shortening was found in LDLr−/− mice. This study also shows that activation of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)/telomerase reverse transcriptase (TERT) pathway, which is the new link between mitochondria and telomere, was involved in the protective effects of catalpol. Further, by using PGC-1α or TERT siRNA in oxLDL-treated macrophages, it is proved that catalpol reduced oxidative stress, telomere function, and related DNA damage at least partly through activating the PGC-1α/TERT pathway. Moreover, dual luciferase activity assay-validated catalpol directly enhanced PGC-1α promoter activity. In conclusion, our study revealed that the PGC-1α/TERT pathway might be a possible therapeutic target in AS and catalpol has highly favorable characteristics for the treatment of AS via modulating this pathway.

scholarly journals Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chao He ◽  
Wei Zhang ◽  
Suobei Li ◽  
Wei Ruan ◽  
Junmei Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Hypoxia Inducible Factor ◽  
Cecal Ligation ◽  
Radical Scavenger ◽  
High Dose ◽  
Beneficial Effects ◽  
Apoptosis And Inflammation

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

scholarly journals Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunke Tan ◽  
Kai Yu ◽  
Lian Liang ◽  
Yuanshan Liu ◽  
Fengqing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Energy Metabolism ◽  
Cardiac Function ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Mitochondrial Activity ◽  
Mitochondrial Energy Metabolism ◽  
Myocardial Oxidative Stress

Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium–glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empagliflozin on cardiac function in rats with myocardial dysfunction after CA. Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 min after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. We found that empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as heart β-hydroxy butyrate dehydrogenase 1 protein expression. Together, these metabolic changes were associated with an increase in cardiac energy metabolism. Therefore, empagliflozin favorably affected cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might benefit patients with myocardial dysfunction after CA.

scholarly journals Protective Role ofPsoralea corylifoliaL. Seed Extract against Hepatic Mitochondrial Dysfunction Induced by Oxidative Stress or Aging

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Eunhui Seo ◽  
Yoon Sin Oh ◽  
Donghee Kim ◽  
Mi-Young Lee ◽  
Sungwook Chae ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Hepg2 Cells ◽  
Peroxisome Proliferator ◽  
Ros Production ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Production ◽  
Genome Damage

The accumulation of oxidative damage and mitochondrial dysfunction is an important factor that contributes to aging. ThePsoralea corylifoliaseeds (PCS), commonly known as “Boh-Gol-Zhee” in Korea, have been used traditionally as a medicinal remedy. We investigated whether an extract of PCS has protective effects on oxidative stress and mitochondrial function in hepatocytes. The PCS extract showed an antisenescence effect on human diploid fibroblasts as evidenced by a decreased expression ofp16INK4amRNA and senescence-associatedβ-galactosidase staining. PCS extract treatment reduced H2O2-induced reactive oxygen species (ROS) production in HepG2 cells, inhibited ROS production in hepatocytes of aged mice, and increased superoxide dismutase activity. In H2O2-treated HepG2 cells, PCS extract treatment recovered ATP production. PCS extract treatment recovered the oxygen consumption rate and inhibited reduction of mitochondrial membrane potential induced by oxidative stress, suggesting improvement of mitochondrial function. In addition, PCS extract treatment recovered peroxisome proliferator-activated receptorγcoactivator 1αand carnitine palmitoyltransferase 1 mRNA and protein expression, and inhibited mitochondrial genome damage. Treatment with the major component of PCS extract, bakuchiol, also recovered mitochondrial dysfunction. On the basis of these results, we conclude that PCS extract inhibits ROS production and mitochondrial dysfunction induced by oxidative stress in hepatocytes.

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