scholarly journals Nicotinamide riboside promotes autolysosome clearance in preventing doxorubicin-induced cardiotoxicity

2019 ◽  
Vol 133 (13) ◽  
pp. 1505-1521 ◽  
Author(s):  
Dong Zheng ◽  
Yi Zhang ◽  
Ming Zheng ◽  
Ting Cao ◽  
Grace Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Myocardial Dysfunction ◽  
Cardiac Injury ◽  
Autophagic Flux ◽  
Protective Effects ◽  
Nicotinamide Riboside ◽  
And Oxidative Stress ◽  
Cultured Cardiomyocytes ◽  
Lysosomal Acidification

Abstract Doxorubicin (DOX) is widely used as a first-line chemotherapeutic drug for various malignancies. However, DOX causes severe cardiotoxicity, which limits its clinical uses. Oxidative stress is one of major contributors to DOX-induced cardiotoxicity. While autophagic flux serves as an important defense mechanism against oxidative stress in cardiomyocytes, recent studies have demonstrated that DOX induces the blockage of autophagic flux, which contributes to DOX cardiotoxicity. The present study investigated whether nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD)+, prevents DOX cardiotoxicity by improving autophagic flux. We report that administration of NR elevated NAD+ levels, and reduced cardiac injury and myocardial dysfunction in DOX-injected mice. These protective effects of NR were recapitulated in cultured cardiomyocytes upon DOX treatment. Mechanistically, NR prevented the blockage of autophagic flux, accumulation of autolysosomes, and oxidative stress in DOX-treated cardiomyocytes, the effects of which were associated with restoration of lysosomal acidification. Furthermore, inhibition of lysosomal acidification or SIRT1 abrogated these protective effects of NR during DOX-induced cardiotoxicity. Collectively, our study shows that NR enhances autolysosome clearance via the NAD+/SIRT1 signaling, thereby preventing DOX-triggered cardiotoxicity.

Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH

2017 ◽  
Vol 9 (415) ◽  
pp. eaam8574 ◽  
Author(s):  
Atze van der Pol ◽  
Andres Gil ◽  
Herman H. W. Silljé ◽  
Jasper Tromp ◽  
Ekaterina S. Ovchinnikova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Myocardial Dysfunction ◽  
Cardiac Injury ◽  
Transcriptional Analysis ◽  
Protective Effects ◽  
Elevated Plasma ◽  
Gene Profile ◽  
Adult Mice ◽  
And Oxidative Stress

In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and on hearts from adult mice with HF. Our screen identified Oplah, encoding for 5-oxoprolinase, a member of the γ-glutamyl cycle that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients, we observed elevated plasma 5-oxoproline, which was associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential diagnostic, prognostic, and therapeutic options in HF.

Role of PI3K/AKT/mTOR Pathway Associated Oxidative Stress and Cardiac Dysfunction in Takotsubo Syndrome

2020 ◽  
Vol 17 (1) ◽  
pp. 35-43
Author(s):  
Shan Mao ◽  
Xianghong Luo ◽  
Yu Li ◽  
Chaorong He ◽  
Fuhua Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Cardiac Injury ◽  
Protective Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Protective Effects ◽  
Takotsubo Syndrome ◽  
Akt Inhibitor

Introduction: Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, but the accurate cause of this syndrome is still unknown. Methods: β-adrenergic agonist isoproterenol (ISO) is used to establish the TTS rats model. TTS rats were treated with or without LY294002 or Rapamycin. The rat cardiomyoblast cell line H9C2 was subjected to infect with constitutively active Akt (myr-Akt) or dominant-negative mutant Akt (dn-Akt) and then, treated with ISO. Cell apoptosis was assessed using the Bax/ Bcl-2 ratio. In addition, reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE). Mitochondrial superoxide generation and membrane potential were assayed by MitoSOX and JC-1 fluorescence intensity. Results: ISO might induce the erratic acute cardiac dysfunction and overexpression of PI3K/AKT/mTOR. Moreover, it also increased the oxidative stress and apoptosis in TTS rats. The Akt inhibitor significantly reversed the cardiac injury effect, which triggered by ISO treatment. In H9C2 cells, the inhibition of Akt provides a protective role against ISO-induced injury by reducing oxidative stress, apoptosis and mitochondrial dysfunction. Conclusion: This study provided new insight into the protective effects of myocardial dysfunction in TTS rats via chronic inhibition of the PI3K/AKT/mTOR expression, which could reduce mitochondrial ROS and oxidative stress-induced apoptosis. PI3K/AKT/mTOR inhibitor could be a therapeutic target to treat cardiovascular dysfunction induced by stress cardiomyopathy.

Effects of Montmorillonite on Growth Performance, Serum Biochemistry and Oxidative Stress of Red-Crowned Crane (Grus japonensis) Fed Mycotoxin-Contaminated Feed

2020 ◽  
Vol 21 (8) ◽  
pp. 626-632 ◽  
Author(s):  
Dawei Liu ◽  
Qinghua Wu ◽  
Hongyi Liu ◽  
Changhu Lu ◽  
Chao Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Performance ◽  
Feed Intake ◽  
Animal Feed ◽  
Bird Species ◽  
Serum Biochemistry ◽  
Protective Effects ◽  
Regular Diet ◽  
Grus Japonensis ◽  
And Oxidative Stress

Background: The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redcrowned crane’s regular diets in China. Objective: This experiment was conducted to investigate the protective effects of mycotoxin binder montmorillonite (Mont) on growth performance, serum biochemistry and oxidative stress parameters of the red-crowned crane. Methods: 16 red-crowned cranes were divided into four groups and fed one of the following diets; a selected diet, regular diet, or the selected diet or regular diet with 0.5% montmorillonite added to the diets. The cranes' parameters of performance, hematology, serum biochemistry and serum oxidative stress were measured. Results: Consuming regular diets decreased the average daily feed intake (ADFI), levels of haemoglobin (Hb), platelet count (PLT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), but increased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK) and lactate dehydrogenase (LDH). The supplementation of 0.5% Mont provided protection for the red-crowned crane in terms of feed intake, serum biochemistry and oxidative stress. Moreover, Mont supplementation had no adverse effect on the health of red-crowned crane. Conclusions: Taken together, these findings suggested that the addition of dietary Mont is effective in improving the health of red-crowned crane.

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

Protective effects of anthocyanin against apoptosis and oxidative stress induced by arsanilic acid in DF-1 cells

2018 ◽  
Vol 46 (1) ◽  
pp. 301-308 ◽  
Author(s):  
Ning Xie ◽  
Na Geng ◽  
Dong Zhou ◽  
Yuliang Xu ◽  
Kangping Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effects ◽  
Arsanilic Acid ◽  
And Oxidative Stress

scholarly journals Salidroside pretreatment protects against myocardial injury induced by heat stroke in mice

2019 ◽  
Vol 47 (10) ◽  
pp. 5229-5238
Author(s):  
Guo-dong Chen ◽  
Heng Fan ◽  
Jian-Hua Zhu
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Troponin I ◽  
Heat Stroke ◽  
Cardiac Injury ◽  
Myocardial Damage ◽  
Thiobarbituric Acid ◽  
Protective Effects ◽  
Creatine Kinase Mb ◽  
Factor Α

Objective To explore the protective effects and mechanisms of salidroside on myocardial injury induced by heat stroke (HS) in mice. Methods We pretreated mice with salidroside for 1 week and then established an HS model by exposure to 41.2°C for 1 hour. We then examined the effects of salidroside on survival. We also assessed the severity of cardiac injury by pathology, and analyzed changes in levels of myocardial injury markers, inflammatory cytokines, and oxidative stress. Results Salidroside pretreatment significantly reduced HS-induced mortality and improved thermoregulatory function. Salidroside also provided significant protection against HS-induced myocardial damage, and decreased the expression levels of cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase. Moreover, salidroside attenuated HS-induced changes in the inflammation markers tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and down-regulated the oxidative stress response indicated by thiobarbituric acid reactant substances, malondialdehyde, reduced glutathione, and superoxide dismutase. Conclusions Salidroside pretreatment protected against HS-induced myocardial damage, potentially via a mechanism involving anti-inflammatory and anti-oxidative effects.

scholarly journals Lysophosphatidylcholine Offsets the Protective Effects of Bone Marrow Mesenchymal Stem Cells on Inflammatory Response and Oxidative Stress Injury of Retinal Endothelial Cells via TLR4/NF-κB Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Haijun Zhao ◽  
Yanhui He
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Inflammatory Response ◽  
Protective Effects ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
And Oxidative Stress

Diabetic retinopathy (DR), as a major cause of blindness worldwide, is one common complication of diabetes mellitus. Inflammatory response and oxidative stress injury of endothelial cells play significant roles in the pathogenesis of DR. The study is aimed at investigating the effects of lysophosphatidylcholine (LPC) on the dysfunction of high glucose- (HG-) treated human retinal microvascular endothelial cells (HRMECs) after being cocultured with bone marrow mesenchymal stem cells (BMSCs) and the underlying regulatory mechanism. Coculture of BMSCs and HRMECs was performed in transwell chambers. The activities of antioxidant-related enzymes and molecules of oxidative stress injury and the contents of inflammatory cytokines were measured by ELISA. Flow cytometry analyzed the apoptosis of treated HRMECs. HRMECs were further treated with 10-50 μg/ml LPC to investigate the effect of LPC on the dysfunction of HRMECs. Western blotting was conducted to evaluate levels of TLR4 and p-NF-κB proteins. We found that BMSCs alleviated HG-induced inflammatory response and oxidative stress injury of HRMECs. Importantly, LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs. Furthermore, LPC upregulated the protein levels of TLR4 and p-NF-κB, activating the TLR4/NF-κB signaling pathway. Overall, our study demonstrated that LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs via TLR4/NF-κB signaling.

Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats

2014 ◽  
Vol 70 (3) ◽  
pp. 713-723 ◽  
Author(s):  
Mohamed Salah Allagui ◽  
Anouer Feriani ◽  
Zouhour Bouoni ◽  
Hichem Alimi ◽  
Jean Claud Murat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Rats ◽  
Protective Effects ◽  
And Oxidative Stress
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