Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients

Background and Purpose: Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH. Methods: This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 µg/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups. Results: In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90±17.63 versus 30.66±32.35, P <0.01) and PHE ratio (1.19±0.73 versus 2.05±1.27, P <0.01). Among clinical factors, time to reach target Richmond Agitation Sedation Scale (5.98 hours [95% CI, 4.82–7.241 versus 8.42 hours], [95% CI, 6.57–10.77], P <0.01) and the length of intensive care unit stays (6.46 days [95% CI, 2.38–10.55 versus 12.66 days], [95% CI, 8.47–16.85], P <0.01) were significantly shortened among patients who received ROS scavengers than among patients who did not receive ROS scavenger. Conclusions: ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study. Registration: URL: https://cris.nih.go.kr/cris/en ; Unique identifier: KCT0004628.

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Clinical aspects of reactive oxygen and nitrogen species

Biochemical Society Symposium ◽

10.1042/bss0710121 ◽

2004 ◽

Vol 71 ◽

pp. 121-133 ◽

Cited By ~ 25

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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Danshensu Rescues Ischemia/Reperfusion Caused Human Hepatocyte Death

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:117-121 ◽

2018 ◽

Vol 17 (2) ◽

pp. 117-121

Author(s):

Sun Maw-Sheng ◽

Liang Chun-Ya ◽

Hsieh Po-Chun ◽

Kuo Chan-Yen

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Caspase 3 ◽

Ischemia Reperfusion ◽

Oxygen Species ◽

Good Strategy ◽

Ros Accumulation ◽

Dichlorofluorescin Diacetate ◽

Hepatocyte Damage ◽

Hepatocyte Death

Apoptosis of hepatocyte, under ischemia/reperfusion (IR) conditions, has been identified as an essential process in the progression of liver transplantation. Under these conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). Additionally, ROS overproduction may induce inflammation. As ROS accumulation appears to cause hepatocyte damage or death, there has been considerable interest in identifying the candidate natural products involved and in developing strategies to reduce oxidative stress. In this study, we use Danshensu as a candidate product to speculate whether has the protective effect on apoptotic hepatocyte upon IR. To speculate the apoptotic phenomena was reversed by Danshensu, we detected the p53, cleaved-caspase 3 expression by western blotting, as well as caspase-3 activity. Additionally, we analyzed the ROS levels by 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining. We also detected the cell viability by WST-1. Results showed that Danshensu alleviated hypoxia-caused cell apoptosis via ROS overproduction. We suggested that Danshensu is a good strategy for treating hepatocyte damage upon IR.

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4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1670759 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 2

Author(s):

Amnah M. Alshangiti ◽

Eszter Tuboly ◽

Shane V. Hegarty ◽

Cathal M. McCarthy ◽

Aideen M. Sullivan ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Cell Death ◽

Cytotoxic Effect ◽

Neuroblastoma Cells ◽

Reactive Oxygen ◽

Prognostic Indicator ◽

Oxygen Species ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

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Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Molecules ◽

10.3390/molecules26144138 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4138

Author(s):

Yeon-Jin Cho ◽

Sun-Hye Choi ◽

Ra-Mi Lee ◽

Han-Sung Cho ◽

Hyewhon Rhim ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Signaling Pathway ◽

Reactive Oxygen ◽

Akt Signaling ◽

Atp Depletion ◽

Oxygen Species ◽

Akt Signaling Pathway ◽

Neuroprotective Effects ◽

Lpa1 Receptor

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

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How to express the antioxidant properties of substances properly?

Chemical Papers ◽

10.1007/s11696-021-01799-1 ◽

2021 ◽

Author(s):

Małgorzata Olszowy-Tomczyk

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Literature Review ◽

Antioxidant Activities ◽

Antioxidant Properties ◽

Reactive Oxygen ◽

The Body ◽

Universal Method ◽

Oxygen Species ◽

Good Tool

AbstractOxidative stress, associated with an imbalance between the oxidants (reactive oxygen species) and the antioxidants in the body, contributes to the development of many diseases. The body’s fight against reactive oxygen species is supported by antioxidants. Nowadays, there are too many analytical methods, but there is no one universal technique for assessing antioxidant properties. Moreover, the applied different ways of expressing the results lead to their incompatibility and unreasonable interpretation. The paper is a literature review concerning the most frequent ways of antioxidant activities expression and for an easy and universal method of the obtained results discussion. This paper is an attempt to point out their disadvantages and advantages. The manuscript can support the searching interpretation of the obtained results which will be a good tool for the development of a number of fields, especially medicine what can help in the future detection and treatment of many serious diseases. Graphic abstract

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Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

Cells ◽

10.3390/cells10020233 ◽

2021 ◽

Vol 10 (2) ◽

pp. 233

Author(s):

Tasuku Konno ◽

Eduardo Pinho Melo ◽

Joseph E. Chambers ◽

Edward Avezov

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Hydrogen Peroxide ◽

Endoplasmic Reticulum ◽

Neurodegenerative Diseases ◽

Antioxidative Enzymes ◽

Redox Reactions ◽

Ros Production ◽

Oxygen Species ◽

Specific Target

Reactive oxygen species (ROS) are produced continuously throughout the cell as products of various redox reactions. Yet these products function as important signal messengers, acting through oxidation of specific target factors. Whilst excess ROS production has the potential to induce oxidative stress, physiological roles of ROS are supported by a spatiotemporal equilibrium between ROS producers and scavengers such as antioxidative enzymes. In the endoplasmic reticulum (ER), hydrogen peroxide (H2O2), a non-radical ROS, is produced through the process of oxidative folding. Utilisation and dysregulation of H2O2, in particular that generated in the ER, affects not only cellular homeostasis but also the longevity of organisms. ROS dysregulation has been implicated in various pathologies including dementia and other neurodegenerative diseases, sanctioning a field of research that strives to better understand cell-intrinsic ROS production. Here we review the organelle-specific ROS-generating and consuming pathways, providing evidence that the ER is a major contributing source of potentially pathologic ROS.

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An example of molecular co-evolution: Reactive oxygen species (ROS) and ROS scavenger levels in Schistosoma mansoni/Biomphalaria glabrata interactions

International Journal for Parasitology ◽

10.1016/j.ijpara.2011.01.007 ◽

2011 ◽

Vol 41 (7) ◽

pp. 721-730 ◽

Cited By ~ 43

Author(s):

Yves Moné ◽

Anne-Cécile Ribou ◽

Céline Cosseau ◽

David Duval ◽

André Théron ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Schistosoma Mansoni ◽

Reactive Oxygen ◽

Biomphalaria Glabrata ◽

Oxygen Species ◽

Ros Scavenger

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The role of oxidative/nitrosative stress in pathogenesis of paracetamol-induced toxic hepatitis

Medicinski pregled ◽

10.2298/mpns1012827r ◽

2010 ◽

Vol 63 (11-12) ◽

pp. 827-832 ◽

Cited By ~ 7

Author(s):

Tatjana Radosavljevic ◽

Dusan Mladenovic ◽

Danijela Vucevic ◽

Rada Jesic-Vukicevic

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Reactive Oxygen Species ◽

Liver Injury ◽

Kupffer Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Severe Liver ◽

Hepatocellular Necrosis

Introduction. Paracetamol is an effective analgesic/antipyretic drug when used at therapeutic doses. However, the overdose of paracetamol can cause severe liver injury and liver necrosis. The mechanism of paracetamol-induced liver injury is still not completely understood. Reactive metabolite formation, depletion of glutathione and alkylation of proteins are the triggers of inhibition of mitochondrial respiration, adenosine triphosphate depletion and mitochondrial oxidant stress leading to hepatocellular necrosis. Role of oxidative stress in paracetamol-induced liver injury. The importance of oxidative stress in paracetamol hepatotoxicity is controversial. Paracetamol induced liver injury cause the formation of reactive oxygen species. The potent sources of reactive oxygen are mitochondria, neutrophils, Kupffer cells and the enzyme xatnine oxidase. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in paracetamol-induced oxidative stress. The production of mitochondrial reactive oxygen species is increased, and the glutathione content is decreased in paracetamol overdose. Oxidative stress in mitochondria leads to mito?chondrial dysfunction with adenosine triphosphate depletion, increase mitochondrial permeability transition, deoxyribonu?cleic acid fragmentation which contribute to the development of hepatocellular necrosis in the liver after paracetamol overdose. Role of Kupffer cells in paracetamol-induced liver injury. Paracetamol activates Kupffer cells, which then release numerous cytokines and signalling molecules, including nitric oxide and superoxide. Kupffer cells are important in peroxynitrite formation. On the other hand, the activated Kupffer cells release anti-inflammatory cytokines. Role of neutrophils in paracetamol-induced liver injury. Paracetamol-induced liver injury leads to the accumulation of neutrophils, which release lysosomal enzymes and generate superoxide anion radicals through the enzyme nicotinamide adenine dinucleotide phosphate oxidase. Hydrogen peroxide, which is influenced by the neutrophil-derived enzyme myeloperoxidase, generates hypochlorus acid as a potent oxidant. Role of peroxynitrite in paracetamol-induced oxidative stress. Superoxide can react with nitric oxide to form peroxynitrite, as a potent oxidant. Nitrotyrosine is formed by the reaction of tyrosine with peroxynitrite in paracetamol hepatotoxicity. Conclusion. Overdose of paracetamol may produce severe liver injury with hepatocellular necrosis. The most important mechanisms of cell injury are metabolic activation of paracetamol, glutathione depletion, alkylation of proteins, especially mitochondrial proteins, and formation of reactive oxygen/nitrogen species.

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Hyperglycemia Induces Generation of Reactive Oxygen Species and Accelerates Apoptotic Cell Death in Salivary Gland Cells

Pathobiology ◽

10.1159/000512639 ◽

2021 ◽

pp. 1-8

Author(s):

Naoyuki Matsumoto ◽

Daisuke Omagari ◽

Ryoko Ushikoshi-Nakayama ◽

Tomoe Yamazaki ◽

Hiroko Inoue ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Salivary Gland ◽

Tissue Injury ◽

Ros Production ◽

Oxygen Species ◽

Saliva Secretion ◽

Salivary Gland Tissue ◽

Gland Tissue

Introduction: Type-2 diabetes mellitus (T2DM) is associated with several systemic vascular symptoms and xerostomia. It is considered that hyperglycemia-induced polyuria and dehydration cause decreased body-water volume, leading to decreased saliva secretion and, ultimately, xerostomia. In T2DM, increased production of reactive oxygen species (ROS) causes tissue damage to vascular endothelial cells as well as epithelial tissue, including pancreas and cornea. Hence, a similar phenomenon may occur in other tissues and glands in a hyperglycemic environment. Methods: Salivary gland tissue injury was examined, using T2DM model mouse (db/db). Transferase‐mediated dUTP nick‐end labeling (TUNEL) was conducted to evaluate tissue injury. The levels of malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine, Bax/Bcl-2 ratio were measured as indicator of oxidative stress. Moreover, in vitro ROS production and cell injury was evaluated by mouse salivary gland-derived normal cells under high-glucose condition culture. Results: In vivo and in vitro analysis showed a higher percentage of TUNEL-positive cells and higher levels of MDA and 8-hydroxy-2′-deoxyguanosine in salivary gland tissue of db/db mice. This suggests damage of saliva secretion-associated lipids and DNA by hyperglycemic-induced oxidative stress. To analyze the mechanism by which hyperglycemia promotes ROS production, mouse salivary gland-derived cells were isolated. The cell culture with high-glucose medium enhanced ROS production and promotes apoptotic and necrotic cell death. Conclusion: These findings suggest a novel mechanism whereby hyperglycemic-induced ROS production promotes salivary gland injury, resulting in hyposalivation.

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