scholarly journals Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zhenjia Yao ◽  
Qinqin Bai ◽  
Gaiqing Wang
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Intracerebral Hemorrhage ◽  
Blood Brain Barrier ◽  
Therapeutic Strategies ◽  
Secondary Brain Injury ◽  
Oxygen Species ◽  
Current State

Oxidative stress (OS) is induced by the accumulation of reactive oxygen species (ROS) following intracerebral hemorrhage (ICH) and plays an important role in secondary brain injury caused by the inflammatory response, apoptosis, autophagy, and blood-brain barrier (BBB) disruption. This review summarizes the current state of knowledge regarding the pathogenic mechanisms of brain injury after ICH, markers for detecting OS, and therapeutic strategies that target OS to mitigate brain injury.

scholarly journals PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Sergio Rius-Pérez ◽  
Isabel Torres-Cuevas ◽  
Iván Millán ◽  
Ángel L. Ortega ◽  
Salvador Pérez
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Metabolic Syndrome ◽  
Inflammatory Response ◽  
Reactive Oxygen ◽  
High Energy ◽  
Low Grade ◽  
Oxygen Species ◽  
Antioxidant Genes ◽  
Integrative View

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a transcriptional coactivator described as a master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation and reactive oxygen species detoxification. PGC-1α is highly expressed in tissues with high energy demands, and it is clearly associated with the pathogenesis of metabolic syndrome and its principal complications including obesity, type 2 diabetes mellitus, cardiovascular disease, and hepatic steatosis. We herein review the molecular pathways regulated by PGC-1α, which connect oxidative stress and mitochondrial metabolism with inflammatory response and metabolic syndrome. PGC-1α regulates the expression of mitochondrial antioxidant genes, including manganese superoxide dismutase, catalase, peroxiredoxin 3 and 5, uncoupling protein 2, thioredoxin 2, and thioredoxin reductase and thus prevents oxidative injury and mitochondrial dysfunction. Dysregulation of PGC-1α alters redox homeostasis in cells and exacerbates inflammatory response, which is commonly accompanied by metabolic disturbances. During inflammation, low levels of PGC-1α downregulate mitochondrial antioxidant gene expression, induce oxidative stress, and promote nuclear factor kappa B activation. In metabolic syndrome, which is characterized by a chronic low grade of inflammation, PGC-1α dysregulation modifies the metabolic properties of tissues by altering mitochondrial function and promoting reactive oxygen species accumulation. In conclusion, PGC-1α acts as an essential node connecting metabolic regulation, redox control, and inflammatory pathways, and it is an interesting therapeutic target that may have significant benefits for a number of metabolic diseases.

scholarly journals Oxymatrine Ameliorates Memory Impairment in Diabetic Rats by Regulating Oxidative Stress and Apoptosis: Involvement of NOX2/NOX4

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yongpan Huang ◽  
Xinliang Li ◽  
Xi Zhang ◽  
Jiayu Tang
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Brain Injury ◽  
Western Blotting ◽  
Caspase 3 ◽  
Memory Function ◽  
Diabetic Rats ◽  
Oxygen Species ◽  
Expression Levels

Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait and has been shown to exhibit a diverse range of pharmacological properties. The aim of the present study was to investigate the role of OMT in diabetic brain injury in vivo and in vitro. Diabetic rats were induced by intraperitoneal injection of a single dose of 65 mg/kg streptozotocin (STZ) and fed a high-fat and high-cholesterol diet. Memory function was assessed using a Morris water maze test. A SH-SY5Y cell injury model was induced by incubation with glucose (30 mM/l) to simulate damage in vitro. The serum fasting blood glucose, insulin, serum S100B, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were analyzed using commercial kits. Morphological changes were observed using Nissl staining and electron microscopy. Cell apoptosis was assessed using Hoechst staining and TUNEL staining. NADPH oxidase (NOX) and caspase-3 activities were determined. The effects of NOX2 and NOX4 knockdown were assessed using small interfering RNA. The expression levels of NOX1, NOX2, and NOX4 were detected using reverse transcription-quantitative PCR and western blotting, and the levels of caspase-3 were detected using western blotting. The diabetic rats exhibited significantly increased plasma glucose, insulin, reactive oxygen species (ROS), S-100B, and MDA levels and decreased SOD levels. Memory function was determined by assessing the percentage of time spent in the target quadrant, the number of times the platform was crossed, escape latency, and mean path length and was found to be significantly reduced in the diabetic rats. Hyperglycemia resulted in notable brain injury, including histological changes and apoptosis in the cortex and hippocampus. The expression levels of NOX2 and NOX4 were significantly upregulated at the protein and mRNA levels, and NOX1 expression was not altered in the diabetic rats. NOX and caspase-3 activities were increased, and caspase-3 expression was upregulated in the brain tissue of diabetic rats. OMT treatment dose-dependently reversed behavioral, biochemical, and molecular changes in the diabetic rats. In vitro, high glucose resulted in increases in reactive oxygen species (ROS), MDA levels, apoptosis, and the expressions of NOX2, NOX4, and caspase-3. siRNA-mediated knockdown of NOX2 and NOX4 decreased NOX2 and NOX4 expression levels, respectively, and reduced ROS levels and apoptosis. The results of the present study suggest that OMT alleviates diabetes-associated cognitive decline, oxidative stress, and apoptosis via NOX2 and NOX4 inhibition.

scholarly journals The Influence of Oxidative Stress on Neurological Outcomes in Spontaneous Intracerebral Hemorrhage

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1615
Author(s):  
Julia Masomi-Bornwasser ◽  
Elena Kurz ◽  
Christina Frenz ◽  
Jan Schmitt ◽  
Dominik M. A. Wesp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Total Antioxidant Status ◽  
Secondary Brain Injury ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Neurological Outcomes ◽  
Total Antioxidant ◽  
Patient’S Outcome ◽  
The Impact

Spontaneous intracerebral hemorrhage (ICH) causes, besides the primary brain injury, a secondary brain injury (SBI), which is induced, amongst other things, by oxidative stress (OS) and inflammation, determining the patient’s outcome. This study aims to assess the impact of OS in plasma and cerebrospinal fluid (CSF) on clinical outcomes in patients with ICH. A total of 19 ICH (volume > 30 cc) patients and 29 control patients were included. From day one until seven, blood and CSF samples were obtained, and ICH volume was calculated. OS markers, like malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-sulfhydryl (GSH), and the total antioxidant status (TAS) were measured. Clinical data on treatment and outcome were determined. Patients with mRS ≤ 4 showed significantly elevated SOD and GSH-Px levels in plasma compared to patients with poor CO (p = 0.004; p = 0.002). Initial increased TAS in plasma and increased MDA in CSF were linked to an unfavorable outcome after six months (p = 0.06, r = 0.45; p = 0.05, r = 0.44). A higher ICH volume was associated with a worse outcome at week six (p = 0.04, r = 0.47). OS plays a significant role in SBI. Larger ICHs, elevated MDA in CSF, and TAS in plasma were associated with a detrimental outcome, whereas higher plasma-SOD and -GSH-Px were associated with a favorable outcome.

scholarly journals Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

2013 ◽  
Vol 34 (5) ◽  
pp. E9 ◽  
Author(s):  
Praveen K. Belur ◽  
Jason J. Chang ◽  
Shuhan He ◽  
Benjamin A. Emanuel ◽  
William J. Mack
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Mass Effect ◽  
Therapeutic Strategies ◽  
Experimental Models ◽  
Thrombin Inhibitors ◽  
Hematoma Expansion ◽  
Secondary Brain Injury ◽  
Limited Efficacy ◽  
Experimental Therapies

Intracerebral hemorrhage (ICH) is associated with a higher degree of morbidity and mortality than other stroke subtypes. Despite this burden, currently approved treatments have demonstrated limited efficacy. To date, therapeutic strategies have principally targeted hematoma expansion and resultant mass effect. However, secondary mechanisms of brain injury are believed to be critical effectors of cell death and neurological outcome following ICH. This article reviews the pathophysiology of secondary brain injury relevant to ICH, examines pertinent experimental models, and highlights emerging therapeutic strategies. Treatment paradigms discussed include thrombin inhibitors, deferoxamine, minocycline, statins, granulocyte-colony stimulating factors, and therapeutic hypothermia. Despite promising experimental and preliminary human data, further studies are warranted prior to effective clinical translation.

scholarly journals Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hyunyun Kim ◽  
Jisoo Yun ◽  
Sang-Mo Kwon
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Stem Cell ◽  
Cardiovascular Diseases ◽  
Progenitor Cells ◽  
Adult Stem Cells ◽  
Reactive Oxygen ◽  
Therapeutic Strategies ◽  
Oxygen Species

Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS) causes cardiovascular diseases (CVDs), atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs), for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence ofex vivoexpanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS-scavenging compounds are crucial and promising therapeutic strategies for vascular repair.

scholarly journals Inflammation and Oxidative Stress in an Obese State and the Protective Effects of Gallic Acid

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 23 ◽  
Author(s):  
Phiwayinkosi Dludla ◽  
Bongani Nkambule ◽  
Babalwa Jack ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Inflammatory Response ◽  
Gallic Acid ◽  
Insulin Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Metabolic Complications ◽  
Enhanced Production ◽  
And Oxidative Stress

Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response and enhanced production of reactive oxygen species. Pro-inflammatory response is known to be associated with the formation of toxic reactive oxygen species and subsequent generation of oxidative stress. Indeed, adipocytes from obese individuals display an altered adipokine profile, with upregulated expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL-6). Interestingly, natural compounds, including phenolic enriched foods are increasingly explored for their ameliorative effects against various metabolic diseases. Of interest is gallic acid, a trihydroxybenzoic acid that has progressively demonstrated robust anti-obesity capabilities in various experimental models. In addition to reducing excessive lipid storage in obese subjects, gallic acid has been shown to specifically target the adipose tissue to suppress lipogenesis, improve insulin signaling, and concomitantly combat raised pro-inflammatory response and oxidative stress. This review will revise mechanisms involved in the pathophysiological effects of inflammation and oxidative stress in an obese state. To better inform on its therapeutic potential and improvement of human health, available evidence reporting on the anti-obesity properties of gallic acid and its derivatives will be discussed, with emphases on its modulatory effect on molecular mechanisms involved in insulin signaling, inflammation and oxidative stress.

scholarly journals Malondialdehyde levels and clinical outcomes assessed by the modified Rankin scale in patients with acute intracerebral hemorrhagic stroke

2021 ◽  
Vol 129 (s2) ◽  
Author(s):  
Abdulloh Machin ◽  
Nurlisa Naila Aulia ◽  
Sita Setyowatie
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Clinical Outcomes ◽  
Hemorrhagic Stroke ◽  
Secondary Brain Injury ◽  
Modified Rankin Scale

Background: Oxidative stress plays an important role in secondary brain injury after a stroke of intracerebral hemorrhage. This study aimed to determine the association between malondialdehyde (MDA) levels with clinical outcomes assessed using the modified Rankin Scale (mRS) in patients with acute intracerebral hemorrhagic stroke

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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