Abstract 892: The Importance of Mitochondrial Oxidative Stress and Integrity of Mitochondrial DNA in Coronary Arteriogenesis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Petra Rocic ◽  
Glenn Wilson ◽  
Inna Shokolenko ◽  
Joy Joseph ◽  
Balaraman Kalyanaraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Drinking Water ◽  
Mitochondrial Dna ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Radioactive Microspheres ◽  
Mt Dna ◽  
Mitochondrial Oxidative Stress ◽  
Localization Sequence

The prediabetic metabolic syndrome (pdMS) leads to many pathological cardiac and vascular phenotypes including impaired arteriogenesis. Mitochondrial (mt) oxidative stress (mtOxStress) is postulated to contribute to the development of such phenotypes, but whether reduction of mtOxStress, or imposition of a maneuver to mimic its effects, would restore or inhibit coronary arteriogenesis (CA), respectively, has not been determined. We tested the hypothesis that in the pdMS, mtOxStress plays a key role in inhibition of coronary arteriogenesis. Lean (LN, n = 6) and obese (OB, n = 6) Zucker obese fatty rats (model of pdMS) were instrumented with a pneumatic snare around the left anterior descending artery (LAD), and subjected to a protocol of repetitive ischemia (RI: 24, 40 sec occlusions/day for 10 days) to stimulate growth. CA was determined from the ratio of flows (radioactive microspheres) measured during LAD occlusion to collateral-dependent and normal zones (CZ/NZ). Prior to RI, CZ/NZ in all groups was less than 0.2 indicating that the native collateral conductance could supply less than 20% of the normally occurring flow during LAD occlusion. After RI, CZ/NZ was 0.82Â ± 0.09 in LN, which was markedly higher (p < 0.05) than that in the OB (0.21Â ± 0.08) indicating impaired CA in the OB rats. To reduce mtOxStress, OB animals (n = 5) were given mito-Quinone (mt-directed free radical scavenger) in drinking water (750 mg/L); this treatment restored CA (CZ/NZ = 0.79Â ± 0.03) comparable to that in LN. Because one manifestation of mt-OxStress is mt-DNA fragmentation, which results in impaired expression of key mt-proteins and compromised mt-function, we determined if administration of a recombinant protein engineered with a TAT sequence to enable intracellular delivery, a mt-localization sequence, and exonuclease ExoIII (mt-tat-ExoIII) to fragment mtDNA would impair coronary arteriogenesis in LN (n = 5). Mt-tat-ExoIII (iv, 0.2 ug/g, every other day) in LN rats impaired CA in response to RI (CZ/NZ = 0.32Â ± 0.09, p < 0.05 vs. LN controls). We conclude that mitochondrial oxidative stress, and its effects on mtDNA integrity, are pivotal in the abrogation of CA in the pdMS.

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia

2006 ◽  
Vol 290 (4) ◽  
pp. H1484-H1492 ◽  
Author(s):  
Kazuhiro Kaneko ◽  
Yoshikazu Yonemitsu ◽  
Takaaki Fujii ◽  
Mitsuho Onimaru ◽  
Chen-Hao Jin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gene Transfer ◽  
Critical Limb Ischemia ◽  
Sendai Virus ◽  
Radical Scavenging ◽  
Limb Ischemia ◽  
Free Radical Scavenger ◽  
Intercellular Adhesion Molecule ◽  
Radical Scavenger ◽  
Intercellular Adhesion Molecule 1

The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.

scholarly journals Role of Cox-2 in Vascular Inflammation: An Experimental Model of Metabolic Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nicolás F. Renna ◽  
Emiliano R. Diez ◽  
Carina Lembo ◽  
Roberto M. Miatello
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Drinking Water ◽  
Experimental Model ◽  
Vascular Remodeling ◽  
Vascular Inflammation ◽  
Left Ventricular ◽  
Wky Rats ◽  
Cox 2

The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n=8each): control (W); W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR): WKY rats receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR): SHR receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases), VCAM-1, and NF-κB by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.

scholarly journals Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 943 ◽  
Author(s):  
Helene Ismail ◽  
Zaynab Shakkour ◽  
Maha Tabet ◽  
Samar Abdelhady ◽  
Abir Kobaisi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Free Radical Scavenger ◽  
Health Concern ◽  
Radical Scavenger ◽  
History Of ◽  
Ionic Imbalance

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

Cellular Cysteine Network and Neurodegeneration

2020 ◽  
pp. 303-325
Author(s):  
Shubhangi H. Pawar ◽  
Vishal S. Gulecha ◽  
Manoj S. Mahajan ◽  
Aman B Upaganiawar ◽  
Chandrashekhar D. Upasani
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Free Radical Scavenger ◽  
Cellular Damage ◽  
Radical Scavenger ◽  
Post Translational Modifications ◽  
Cellular Defense ◽  
Brain Antioxidants ◽  
The Brain ◽  
Oxidative Species

Oxidative stress is strongly linked to neurodegeneration and oxidative species can modify many amino acids and proteins in the brain. Cysteine amino acid is most susceptible to oxidative post-translational modifications (PTMs). Reversible or irreversible cysteine PTMs can cause dyshomeostasis, which further continued to cellular damage. Many cysteine dependent proteins and many non-proteins using cysteine as their structural components are affected by oxidative stress. Several cysteine dependent enzymes are acting as antioxidants. Cysteine is a major contributor to glutathione (GSH) and superoxide dismutase (SOD) synthesis. Cysteine precursor N-acetylcysteine (NAC) supplementation is proven as a potent free radical scavenger and increase brain antioxidants and subsequently potentiates the natural antioxidant cellular defense mechanism. Thus, in this chapter, the authors explore the linkage of cellular cysteine networks and neurodegenerative disorders.

Mitochondrial oxidative stress and the metabolic syndrome

2012 ◽  
Vol 23 (9) ◽  
pp. 429-434 ◽  
Author(s):  
Andrew M. James ◽  
Yvonne Collins ◽  
Angela Logan ◽  
Michael P. Murphy
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Mitochondrial Oxidative Stress ◽  
The Metabolic Syndrome

scholarly journals Therapeutic Time Window for Edaravone Treatment of Traumatic Brain Injury in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Kazuyuki Miyamoto ◽  
Hirokazu Ohtaki ◽  
Kenji Dohi ◽  
Tomomi Tsumuraya ◽  
Dandan Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Death ◽  
Time Window ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Therapeutic Time Window

Traumatic brain injury (TBI) is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS) production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI). Edaravone (3.0 mg/kg), or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2∙-) as a marker of ROS, of nitrotyrosine (NT) as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease inO2∙-levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI.

scholarly journals Day and Night GSH and MDA Levels in Healthy Adults and Effects of Different Doses of Melatonin on These Parameters

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shilpa Chakravarty ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Membrane Lipid ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Secretory Product ◽  
Therapeutic Implications ◽  
Antioxidative Function ◽  
Reliable Marker

The pineal secretory product melatonin (chemically, N-acetyl-5-methoxytryptamine) acts as an effective antioxidant and free-radical scavenger and plays an important role in several physiological functions such as sleep induction, immunomodulation, cardiovascular protection, thermoregulation, neuroprotection, tumor-suppression and oncostasis. Membrane lipid-peroxidation in terms of malondialdehyde (MDA) and intracellular glutathione (GSH) is considered to be a reliable marker of oxidative stress. The present work was undertaken to study the modulating effect of melatonin on MDA and GSH in human erythrocytes during day and night. Our observation shows the modulation of these two biomarkers by melatonin, and this may have important therapeutic implications.In vitrodose-dependent effect of melatonin also showed variation during day and night. We explain our observations on the basis of melatonin's antioxidative function and its effect on the fluidity of plasma membrane of red blood cells. Rhythmic modulation of MDA and GSH contents emphasized the role of melatonin as an antioxidant and its function against oxidative stress.

scholarly journals Melatonin protects the mouse testis against heat-induced damage

2020 ◽  
Vol 26 (2) ◽  
pp. 65-79 ◽  
Author(s):  
Pengfei Zhang ◽  
Yi Zheng ◽  
Yinghua Lv ◽  
Fuyuan Li ◽  
Lihong Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Stress ◽  
Male Fertility ◽  
Reactive Oxygen Species Generation ◽  
Free Radical Scavenger ◽  
Testicular Atrophy ◽  
Therapeutic Drug ◽  
Radical Scavenger ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Abstract Spermatogenesis, an intricate process occurring in the testis, is responsible for ongoing production of spermatozoa and thus the cornerstone of lifelong male fertility. In the testis, spermatogenesis occurs optimally at a temperature 2–4°C lower than that of the core body. Increased scrotal temperature generates testicular heat stress and later causes testicular atrophy and spermatogenic arrest, resulting in a lower sperm yield and therefore impaired male fertility. Melatonin (N-acetyl-5-methoxytryptamine), a small neuro-hormone synthesized and secreted by the pineal gland and the testis, is widely known as a potent free-radical scavenger; it has been reported that melatonin protects the testis against inflammation and reactive oxygen species generation thereby playing anti-inflammatory, -oxidative and -apoptotic roles in the testis. Nevertheless, the role of melatonin in the testicular response to heat stress has not been studied. Here, by employing a mouse model of testicular hyperthermia, we systematically investigated the testicular response to heat stress as well as the occurrence of autophagy, apoptosis and oxidative stress in the testis. Importantly, we found that pre-treatment with melatonin attenuated heat-induced apoptosis and oxidative stress in the testis. Also, post-treatment with melatonin promoted recovery of the testes from heat-induced damage, probably by maintaining the integrity of the Sertoli cell tight-junction. Thus, we for the first time provide the proof of concept that melatonin can protect the testis against heat-induced damage, supporting the potential future use of melatonin as a therapeutic drug in men for sub/infertility incurred by various testicular hyperthermia factors.

scholarly journals Use of Melatonin in Oxidative Stress Related Neonatal Diseases

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 477
Author(s):  
Gabriella D’Angelo ◽  
Roberto Chimenz ◽  
Russel J. Reiter ◽  
Eloisa Gitto
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Defense ◽  
Perinatal Period ◽  
Oxygen Radical ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Perinatal Brain Injury ◽  
Radical Generation ◽  
Prophylactic Use

Reactive oxygen species have a crucial role in the pathogenesis of perinatal diseases. Exposure to inflammation, infections, or high oxygen concentrations is frequent in preterm infants, who have high free iron levels that enhance toxic radical generation and diminish antioxidant defense. The peculiar susceptibility of newborns to oxidative stress supports the prophylactic use of melatonin in preventing or decreasing oxidative stress-mediated diseases. Melatonin, an effective direct free-radical scavenger, easily diffuses through biological membranes and exerts pleiotropic activity everywhere. Multiple investigations have assessed the effectiveness of melatonin to reduce the “oxygen radical diseases of newborn” including perinatal brain injury, sepsis, chronic lung disease (CLD), and necrotizing enterocolitis (NEC). Further studies are still awaited to test melatonin activity during perinatal period.

Pleiotropic roles of melatonin against oxidative stress mediated tissue injury in the gastrointestinal tract: An overview

2019 ◽  
Vol 2 (2) ◽  
pp. 158-184 ◽  
Author(s):  
Palash K Pal ◽  
Bharati Bhattacharjee ◽  
Aindrila Chattopadhyay ◽  
Debasish Bandyopadhyay
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Gi Tract ◽  
Pathological Conditions

The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress.  In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.

Sign in / Sign up

Export Citation Format

Share Document