Abstract 132: A Novel Hydrogen Sulfide (H 2 S) Prodrug, SG1002, Protects Against Myocardial Oxidative Damage and Hypertrophic Signaling via Induction of Cystathionine Β-Synthase (CBS) and Antioxidant Proteins

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Kazi N Islam ◽  
Erminia Donnarumma ◽  
Erinn Donnelly ◽  
David J Lefer
Keyword(s):  
Oxidative Stress ◽  
Clinical Utility ◽  
Culture Media ◽  
Therapeutic Strategies ◽  
Oxidation Products ◽  
Cellular Damage ◽  
Serum Starvation ◽  
Antioxidant Proteins ◽  
Hypertrophic Signaling ◽  
Cells Cultured

Background: Endogenously produced H 2 S is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H 2 S levels have proven cardioprotective in models of acute myocardial infarction and heart failure (HF). The present study was under taken to investigate the effects of a novel H 2 S prodrug, SG1002, on stress induced hypertrophic signaling in murine HL1 cardiomyocytes. Methods: HL1 cells were maintained either in serum starvation (1%) or serum containing (10%) media followed by treatment either with SG1002 or H 2 O 2 , or endothelin-1 (ET-1)/phenylephrine (Phe) or in combination. Treated cells were analyzed for specific experimental needs. Results: SG1002 significantly increased cellular levels of the H 2 S producing enzyme, CBS, as well as production of H 2 S and nitrosothiol in HL1 cells cultured both in serum starvation or serum containing media. SG1002 significantly inhibited H 2 O 2 and ET-1/Phe induced oxidative stress in both culture media as measured by advanced protein oxidation products and MDA levels. Expression of ANP and BNP were markedly attenuated by SG1002 treatment. Cells cultured in media supplemented with serum containing H 2 O 2 /(ET-1 or Phe) or in 1% serum exhibited decreased levels of CBS, SOD1, and catalase. When the HL1 cells were coincubated with SG1002 cellular damage from oxidative stress was significantly attenuated accompanied by an increase in CBS expression. Conclusion: Our data clearly demonstrate that SG1002 attenuates myocardial cellular damage via increasing antioxidant proteins. SG1002 directly increases H 2 S levels and upregulates CBS. Studies are currently underway to evaluate the clinical utility of SG1002 in HF.

scholarly journals H2S Prodrug, SG-1002, Protects Against Myocardial Oxidative Damage and Hypertrophy via Induction of Cystathionine β-Synthase and Antioxidant Proteins

2021 ◽  
Author(s):  
Rahib K. Islam ◽  
Erinn Donnelly ◽  
Fokhrul Hossain ◽  
Jason D. Gardner ◽  
Kazi N. Islam
Keyword(s):  
Oxidative Damage ◽  
Natriuretic Peptide ◽  
Therapeutic Strategies ◽  
Serum Starvation ◽  
Protein Markers ◽  
Cardiac Muscle Cells ◽  
Protein Levels ◽  
Antioxidant Protein ◽  
Antioxidant Proteins ◽  
Hypertrophic Signaling

AbstractEndogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, cystathionine β-synthase (CBS) as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase and decreased oxidative stress. SG-1002 also decreased the expression of hypertrophic/HF protein markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in stressed HL-1 cells. Treatment with SG-1002 caused a significant induction of cell viability and a marked reduction of cellular cytotoxicity in HL-1 cells under serum starvation incubated or with H2O2. Experimental results of this study suggest that SG-1002 attenuates myocardial cellular oxidative damage and/or hypertrophic signaling via increasing H2S levels or H2S producing enzyme, CBS and antioxidant proteins.

scholarly journals Oxidative Stress and Inflammation in Renal and Cardiovascular Complications of Diabetes

Biology ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 18
Author(s):  
Amelia Charlton ◽  
Jessica Garzarella ◽  
Karin A. M. Jandeleit-Dahm ◽  
Jay C. Jha
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Tissue Injury ◽  
Cardiovascular Complications ◽  
Therapeutic Strategies ◽  
Cellular Damage ◽  
Antioxidant Defenses ◽  
Pathological State ◽  
Oxygen Species ◽  
Emerging Therapies

Oxidative stress and inflammation are considered major drivers in the pathogenesis of diabetic complications, including renal and cardiovascular disease. A symbiotic relationship also appears to exist between oxidative stress and inflammation. Several emerging therapies target these crucial pathways, to alleviate the burden of the aforementioned diseases. Oxidative stress refers to an imbalance between reactive oxygen species (ROS) and antioxidant defenses, a pathological state which not only leads to direct cellular damage but also an inflammatory cascade that further perpetuates tissue injury. Emerging therapeutic strategies tackle these pathways in a variety of ways, from increasing antioxidant defenses (antioxidants and Nrf2 activators) to reducing ROS production (NADPH oxidase inhibitors and XO inhibitors) or inhibiting the associated inflammatory pathways (NLRP3 inflammasome inhibitors, lipoxins, GLP-1 receptor agonists, and AT-1 receptor antagonists). This review summarizes the mechanisms by which oxidative stress and inflammation contribute to and perpetuate diabetes associated renal and cardiovascular disease along with the therapeutic strategies which target these pathways to provide reno and cardiovascular protection in the setting of diabetes.

scholarly journals Biomarkers of Oxidative Stress in Metabolic Syndrome and Associated Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Rosa Vona ◽  
Lucrezia Gambardella ◽  
Camilla Cittadini ◽  
Elisabetta Straface ◽  
Donatella Pietraforte
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Natural Antioxidants ◽  
Therapeutic Strategies ◽  
Oxidation Products ◽  
Antioxidant Defenses ◽  
Antioxidant Systems ◽  
Associated Diseases ◽  
Lipid Oxidation Products

Metabolic syndrome (MS) represents worldwide public health issue characterized by a set of cardiovascular risk factors including obesity, diabetes, dyslipidemia, hypertension, and impaired glucose tolerance. The link between the MS and the associated diseases is represented by oxidative stress (OS) and by the intracellular redox imbalance, both caused by the persistence of chronic inflammatory conditions that characterize MS. The increase in oxidizing species formation in MS has been accepted as a major underlying mechanism for mitochondrial dysfunction, accumulation of protein and lipid oxidation products, and impairment of the antioxidant systems. These oxidative modifications are recognized as relevant OS biomarkers potentially able to (i) clarify the role of reactive oxygen and nitrogen species in the etiology of the MS, (ii) contribute to the diagnosis/evaluation of the disease’s severity, and (iii) evaluate the utility of possible therapeutic strategies based on natural antioxidants. The antioxidant therapies indeed could be able to (i) counteract systemic as well as mitochondrial-derived OS, (ii) enhance the endogenous antioxidant defenses, (iii) alleviate MS symptoms, and (iv) prevent the complications linked to MS-derived cardiovascular diseases. The focus of this review is to summarize the current knowledge about the role of OS in the development of metabolic alterations characterizing MS, with particular regard to the occurrence of OS-correlated biomarkers, as well as to the use of therapeutic strategies based on natural antioxidants.

Known Hepatoprotectors Act as Antioxidants and Immune Stimulators in Stressed Mice: Perspectives in Animal Health Care

2019 ◽  
Vol 24 (40) ◽  
pp. 4825-4837 ◽  
Author(s):  
Gustavo Alberto de la Riva ◽  
Francisco Javier López Mendoza ◽  
Guillermin Agüero-Chapin
Keyword(s):  
Oxidative Stress ◽  
Animal Health ◽  
Cellular Damage ◽  
Farm Animals ◽  
Physiological Status ◽  
Stress Markers ◽  
Glutathione Peroxidases ◽  
Transport Chain ◽  
Exogenous Compounds ◽  
Relationship Of

Background: Oxygen is involved in a variety of physiological reactions in aerobic organisms, such as those produced in the electron transport chain, hydroxylation, and oxygenation. Reactive oxygen species (ROS) are naturally formed as byproducts from these previously reactions involving the O2 molecule; they are made up of superoxide anion (O2−), hydroxyl radical (HO−), hydrogen peroxide (H2O2), nitric oxide (NO), peroxyl (ROO−), and reactive aldehyde (ROCH). Under certain environmental stress conditions, ROS are accumulated causing cellular damage but also triggering the overexpression of several enzyme classes such as superoxide dismutases (SOD), catalases (CAT) and glutathione peroxidases (GPx), which represent an important intrinsic antioxidant defence line. Liver is a key organ in vertebrates including farm animals and human. The oxidative stress plays an important role in systemic malfunctions including hepatic, renal and immunological, disorders. Methods: This review presents a brief update about the relationship of oxidative stress with hepatic, renal and immunological malfunctions in stressed organisms. Cellular and exogenous hepatoprotective compounds share also the ability to scavenge ROS acting as antioxidants and in many cases as stimulators of immune response in stressed organisms. We present the effect of some hepatoprotectors on the hepatic, renal and immunological function in stressed mice by the jointed evaluation of biological and oxidative stress markers. Conclusion: Hepatoprotective effect of several exogenous compounds is very associated with their antioxidant capacity. This fact is relevant for keeping oxidant/antioxidant balance in the respective organs, but also for maintaining the physiological status of the whole organism.

Alpha-1-Antichymotrypsin: a Common Player for Type 2 Diabetes and Alzheimer's Disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Regulatory Networks ◽  
Therapeutic Strategies ◽  
Oxidative Stresses ◽  
Bibliographic Search ◽  
And Oxidative Stress

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

scholarly journals Oxidative Stress Biomarkers in Urine of Metal Carpentry Workers Can Be Diagnostic for Occupational Exposure to Low Level of Welding Fumes from Associated Metals

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3167
Author(s):  
Flavia Buonaurio ◽  
Maria Luisa Astolfi ◽  
Daniela Pigini ◽  
Giovanna Tranfo ◽  
Silvia Canepari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Occupational Exposure ◽  
Oxidation Products ◽  
Control Group ◽  
Welding Fumes ◽  
Oxidative Stress Biomarkers ◽  
Limit Values ◽  
Stress Biomarkers ◽  
Specificity And Sensitivity ◽  
The Impact

Urinary concentrations of 16 different exposure biomarkers to metals were determined at the beginning and at the end of a working shift on a group of workers in the metal carpentry industry. Five different oxidative stress biomarkers were also measured, such as the oxidation products of RNA and DNA metabolized and excreted in the urine. The results of workers exposed to metals were compared to those of a control group. The metal concentrations found in these workers were well below the occupational exposure limit values and exceeded the mean concentrations of the same metals in the urine of the control group by a factor of four at maximum. Barium (Ba), mercury (Hg), lead (Pb) and strontium (Sr) were correlated with the RNA oxidative stress biomarker, 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), which was found able to discriminate exposed workers from controls with a high level of specificity and sensitivity. The power of this early diagnostic technique was assessed by means of the ROC curve. Ba, rubidium (Rb), Sr, tellurium (Te), and vanadium (V) were correlated with the level of the protein oxidation biomarker 3-Nitrotyrosine (3-NO2Tyr), and Ba, beryllium (Be), copper (Cu), and Rb with 5-methylcytidine (5-MeCyt), an epigenetic marker of RNA damage. These effect biomarkers can help in identifying those workers that can be defined as “occupationally exposed” even at low exposure levels, and they can provide information about the impact that such doses have on their health.

scholarly journals Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5995
Author(s):  
Chand Basha Davuljigari ◽  
Frederick Adams Ekuban ◽  
Cai Zong ◽  
Alzahraa A. M. Fergany ◽  
Kota Morikawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Hepatic Necrosis ◽  
Related Factor ◽  
Necrosis Factor Alpha ◽  
Adult Mice ◽  
Nrf2 Signaling Pathway ◽  
Antioxidant Proteins ◽  
Oxide Synthase

Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity.

scholarly journals The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 552
Author(s):  
Jasmine Harley ◽  
Benjamin E. Clarke ◽  
Rickie Patani
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Mitochondrial Dysfunction ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Therapeutic Strategies ◽  
Lateral Sclerosis

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

Sign in / Sign up

Export Citation Format

Share Document