Antioxidants

Research

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18 pages, 3360 KiB

Open AccessArticle

Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status

by Hassan Dakik, Maya El Dor, Joan Leclerc, Farah Kouzi, Ali Nehme, Margaux Deynoux, Christelle Debeissat, Georges Khamis, Elfi Ducrocq, Aida Ibrik, Marie-José Stasia, Houssam Raad, Hamid Reza Rezvani, Fabrice Gouilleux, Kazem Zibara, Olivier Herault and Frédéric Mazurier

Antioxidants 2021, 10(3), 498; https://doi.org/10.3390/antiox10030498 - 23 Mar 2021

Cited by 11 | Viewed by 3093

Abstract

In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the [...] Read more.

In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function. Although it has been reported in AML initiation and development, the contribution of NOX to the ROS production in AML remains to be clarified. The aim of this study was to investigate the NOX expression and function in AML, and to examine the role of NOX in blast proliferation and differentiation. First, we interrogated the NOX expression in primary cells from public datasets, and investigated their association with prognostic markers. Next, we explored the NOX expression and activity in AML cell lines, and studied the impact of NOX knockdown on cell proliferation and differentiation. We found that NOX2 is ubiquitously expressed in AML blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages; however, it is less expressed in LSCs and in relapsed AML. This is consistent with an increased expression throughout normal hematopoietic differentiation, and is reflected in AML cell lines. Nevertheless, no endogenous NOX activity could be detected in the absence of PMA stimulation. Furthermore, CYBB knockdown, although hampering induced NOX2 activity, did not affect the proliferation and differentiation of THP-1 and HL-60 cells. In summary, our data suggest that NOX2 is a marker of AML blast differentiation, while AML cell lines lack any NOX2 endogenous activity. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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14 pages, 2590 KiB

Open AccessArticle

Identifying a Role of Red and White Wine Extracts in Counteracting Skin Aging: Effects of Antioxidants on Fibroblast Behavior

by Sara Cruciani, Margherita Trenta, Giovanna Rassu, Giuseppe Garroni, Giacomo Luigi Petretto, Carlo Ventura, Margherita Maioli and Giorgio Pintore

Antioxidants 2021, 10(2), 227; https://doi.org/10.3390/antiox10020227 - 3 Feb 2021

Cited by 7 | Viewed by 4104

Abstract

Dermal fibroblasts are the main actor in many proteins’ secretion, including collagen, preserving skin function. Free radicals are involved in skin aging and damages involving different cellular components. The imbalance between reactive oxygen species (ROS) amount and natural antioxidant enzymes negatively affects skin [...] Read more.

Dermal fibroblasts are the main actor in many proteins’ secretion, including collagen, preserving skin function. Free radicals are involved in skin aging and damages involving different cellular components. The imbalance between reactive oxygen species (ROS) amount and natural antioxidant enzymes negatively affects skin homeostasis. Natural compounds have recently emerged as a potential anti-aging tool in tissue regeneration. In the present paper we evaluated the antioxidant activity of white and red wines, considering their probable use, as raw materials, for the formulation of cosmetic products with anti-aging properties. We studied a method that would allow the removal of the alcoholic fraction of wines and determined their composition by LC-MS analysis. We then tested the possible cytotoxic effects of red and white wines on fibroblasts by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, and their antioxidant activity by the catalase activity test in stressing conditions. Finally, we evaluated their anti-aging potential through the β-galactosidase colorimetric assay. Our results showed that wine extracts exhibit a remarkable antioxidant and anti-aging activity, especially on cells exposed to a marked stressful event. These properties could suggest their possible application as cosmetical products for skin regeneration. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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17 pages, 4052 KiB

Open AccessArticle

Vascular Cells Proteome Associated with Bradykinin and Leptin Inflammation and Oxidative Stress Signals

by Moustafa Al Hariri, Miran A. Jaffa, Richard Saoud, Jingfu Zhao, Rui Zhu, Aneese A. Jaffa, Ghewa A. El-Achkar, Mayssam Moussa, Firas Kobeissy, Anwarul Hassan, Fuad N. Ziyadeh, Yehia Mechref and Ayad A. Jaffa

Antioxidants 2020, 9(12), 1251; https://doi.org/10.3390/antiox9121251 - 9 Dec 2020

Cited by 5 | Viewed by 2177

Abstract

Among the primary contributors to cardiovascular diseases are inflammation and oxidative imbalance within the vessel walls as well as the fibrosis of rat aortic smooth muscle cell (RASMC). Bradykinin (BK) and leptin are inflammatory modulators that are linked to vascular injury. In this [...] Read more.

Among the primary contributors to cardiovascular diseases are inflammation and oxidative imbalance within the vessel walls as well as the fibrosis of rat aortic smooth muscle cell (RASMC). Bradykinin (BK) and leptin are inflammatory modulators that are linked to vascular injury. In this study, we employed tandem LC-MS/MS to identify protein signatures that encompass protein abundance in RASMC treated with BK or leptin followed by systems biology analyses to gain insight into the biological pathways and processes linked to vascular remodeling. In the study, 1837 proteins were identified in control untreated RASMC. BK altered the expression of 72 (4%) and 120 (6.5%) proteins, whereas leptin altered the expression of 189 (10.2%) and 127 (6.5%) proteins after 24 and 48 h, respectively, compared to control RASMC. BK increased the protein abundance of leptin receptor, transforming growth factor-β. On the other hand, leptin increased the protein abundance of plasminogen activator inhibitor 1 but decreased the protein abundance of cofilin. BK and leptin induced the expression of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) and pathway analysis revealed the activation of mitogen-activated protein kinases (MAPKs) and AKT pathways. The proteome profile in response to BK and leptin revealed mechanistic interplay of multiple processes that modulate inflammation and oxidative stress signals in the vasculature. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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15 pages, 444 KiB

Open AccessArticle

Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report

by Alessandro G. Fois, Elisabetta Sotgiu, Valentina Scano, Silvia Negri, Sabrina Mellino, Elisabetta Zinellu, Pietro Pirina, Gianfranco Pintus, Ciriaco Carru, Arduino A. Mangoni and Angelo Zinellu

Antioxidants 2020, 9(11), 1064; https://doi.org/10.3390/antiox9111064 - 30 Oct 2020

Cited by 20 | Viewed by 3147

Abstract

Introduction: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. Methods: Systemic circulating markers of oxidative stress [nuclear [...] Read more.

Introduction: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. Methods: Systemic circulating markers of oxidative stress [nuclear factor erythroid 2–related factor 2 (Nrf2), thiobarbituric acid- reactive substances (TBARS), homocysteine (Hcy), cysteine (Cys), asymmetric dimethylarginine (ADMA) and ADMA/Arginine ratio, glutathione (GSH), plasma protein –SH (PSH), and taurine (Tau)] and inflammation [Kynurenine (Kyn), Tryptophan (Trp) and Kyn/Trp ratio] were measured at baseline and after 24-week treatment in 18 IPF patients (10 treated with pirfenidone and 8 with nintedanib) and in 18 age- and sex-matched healthy controls. Results: Compared to controls, IPF patients had significantly lower concentrations of reduced blood GSH (457 ± 73 µmol/L vs 880 ± 212 µmol/L, p < 0.001) and plasma PSH (4.24 ± 0.95 µmol/g prot vs 5.28 ± 1.35 µmol/g prot, p = 0.012). Pirfenidone treatment significantly decreased the Kyn/Trp ratio (0.030 ± 0.011 baseline vs 0.025 ± 0.010 post-treatment, p = 0.048) whilst nintedanib treatment significantly increased blood GSH (486 ± 70 μmol/L vs 723 ± 194 μmol/L, p = 0.006) and reduced ADMA concentrations (0.501 ± 0.094 vs. 0.468 ± 0.071 μmol/L, p = 0.024). Conclusion: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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Review

Jump to: Research

28 pages, 1815 KiB

Open AccessReview

The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications

by Qinhong Wang and Rahima Zennadi

Antioxidants 2021, 10(10), 1608; https://doi.org/10.3390/antiox10101608 - 13 Oct 2021

Cited by 22 | Viewed by 4843

Abstract

Sickle cell disease (SCD) is an inherited monogenic disorder and the most common severe hemoglobinopathy in the world. SCD is characterized by a point mutation in the β-globin gene, which results in hemoglobin (Hb) S production, leading to a variety of mechanistic and [...] Read more.

Sickle cell disease (SCD) is an inherited monogenic disorder and the most common severe hemoglobinopathy in the world. SCD is characterized by a point mutation in the β-globin gene, which results in hemoglobin (Hb) S production, leading to a variety of mechanistic and phenotypic changes within the sickle red blood cell (RBC). In SCD, the sickle RBCs are the root cause of the disease and they are a primary source of oxidative stress since sickle RBC redox state is compromised due to an imbalance between prooxidants and antioxidants. This imbalance in redox state is a result of a continuous production of reactive oxygen species (ROS) within the sickle RBC caused by the constant endogenous Hb autoxidation and NADPH oxidase activation, as well as by a deficiency in the antioxidant defense system. Accumulation of non-neutralized ROS within the sickle RBCs affects RBC membrane structure and function, leading to membrane integrity deficiency, low deformability, phosphatidylserine exposure, and release of micro-vesicles. These oxidative stress-associated RBC phenotypic modifications consequently evoke a myriad of physiological changes involved in multi-system manifestations. Thus, RBC oxidative stress in SCD can ultimately instigate major processes involved in organ damage. The critical role of the sickle RBC ROS production and its regulation in SCD pathophysiology are discussed here. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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21 pages, 2712 KiB

Open AccessReview

Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells

by Nadezhda Barvitenko, Elisaveta Skverchinskaya, Alfons Lawen, Elena Matteucci, Carlota Saldanha, Giuseppe Uras, Alessia Manca, Muhammad Aslam and Antonella Pantaleo

Antioxidants 2021, 10(6), 904; https://doi.org/10.3390/antiox10060904 - 3 Jun 2021

Cited by 2 | Viewed by 3119

Abstract

Endothelial cells (ECs) are exposed to molecular dioxygen and its derivative reactive oxygen species (ROS). ROS are now well established as important signaling messengers. Excessive production of ROS, however, results in oxidative stress, a significant contributor to the development of numerous diseases. Here, [...] Read more.

Endothelial cells (ECs) are exposed to molecular dioxygen and its derivative reactive oxygen species (ROS). ROS are now well established as important signaling messengers. Excessive production of ROS, however, results in oxidative stress, a significant contributor to the development of numerous diseases. Here, we analyze the experimental data and theoretical concepts concerning positive pro-survival effects of ROS on signaling pathways in endothelial cells (ECs). Our analysis of the available experimental data suggests possible positive roles of ROS in induction of pro-survival pathways, downstream of the G_i-protein-coupled receptors, which mimics insulin signaling and prevention or improvement of the endothelial dysfunction. It is, however, doubtful, whether ROS can contribute to the stabilization of the endothelial barrier. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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18 pages, 1546 KiB

Open AccessReview

The Enzymatic and Non-Enzymatic Function of Myeloperoxidase (MPO) in Inflammatory Communication

by Yulia Kargapolova, Simon Geißen, Ruiyuan Zheng, Stephan Baldus, Holger Winkels and Matti Adam

Antioxidants 2021, 10(4), 562; https://doi.org/10.3390/antiox10040562 - 5 Apr 2021

Cited by 39 | Viewed by 4506

Abstract

Myeloperoxidase is a signature enzyme of polymorphonuclear neutrophils in mice and humans. Being a component of circulating white blood cells, myeloperoxidase plays multiple roles in various organs and tissues and facilitates their crosstalk. Here, we describe the current knowledge on the tissue- and [...] Read more.

Myeloperoxidase is a signature enzyme of polymorphonuclear neutrophils in mice and humans. Being a component of circulating white blood cells, myeloperoxidase plays multiple roles in various organs and tissues and facilitates their crosstalk. Here, we describe the current knowledge on the tissue- and lineage-specific expression of myeloperoxidase, its well-studied enzymatic activity and incoherently understood non-enzymatic role in various cell types and tissues. Further, we elaborate on Myeloperoxidase (MPO) in the complex context of cardiovascular disease, innate and autoimmune response, development and progression of cancer and neurodegenerative diseases. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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27 pages, 1400 KiB

Open AccessReview

Pharmacological and Antioxidant Activities of Rhus coriaria L. (Sumac)

by Halima Alsamri, Khawlah Athamneh, Gianfranco Pintus, Ali H. Eid and Rabah Iratni

Antioxidants 2021, 10(1), 73; https://doi.org/10.3390/antiox10010073 - 8 Jan 2021

Cited by 72 | Viewed by 8184

Abstract

Rhus coriaria L. (Anacardiaceae), commonly known as sumac, is a commonly used spice, condiment, and flavoring agent, especially in the Mediterranean region. Owing to its bountiful beneficial values, sumac has been used in traditional medicine for the management and treatment of many ailments [...] Read more.

Rhus coriaria L. (Anacardiaceae), commonly known as sumac, is a commonly used spice, condiment, and flavoring agent, especially in the Mediterranean region. Owing to its bountiful beneficial values, sumac has been used in traditional medicine for the management and treatment of many ailments including hemorrhoids, wound healing, diarrhea, ulcer, and eye inflammation. This plant is rich in various classes of phytochemicals including flavonoids, tannins, polyphenolic compounds, organic acids, and many others. By virtue of its bioactive, Rhus coriaria possesses powerful antioxidant capacities that have ameliorative and therapeutic benefits for many common diseases including cardiovascular disease, diabetes, and cancer. This review describes the phytochemical properties of R. coriaria and then focuses on the potent antioxidant capacities of sumac. We then dissect the cellular and molecular mechanisms of sumac’s action in modulating many pathophysiological instigators. We show how accumulating evidence supports the antibacterial, antinociceptive, antidiabetic, cardioprotective, neuroprotective, and anticancer effects of this plant, especially that toxicity studies show that sumac is very safe to consume by humans and has little toxicity. Taken together, the findings we summarize here support the utilization of this plant as an attractive target for drug discovery. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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18 pages, 2047 KiB

Open AccessReview

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

by Helene Ismail, Zaynab Shakkour, Maha Tabet, Samar Abdelhady, Abir Kobaisi, Reem Abedi, Leila Nasrallah, Gianfranco Pintus, Yusra Al-Dhaheri, Stefania Mondello, Riyad El-Khoury, Ali H. Eid, Firas Kobeissy and Johnny Salameh

Antioxidants 2020, 9(10), 943; https://doi.org/10.3390/antiox9100943 - 1 Oct 2020

Cited by 70 | Viewed by 7721

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Not Just Stress: The Role of Oxidation from Blood and Tissue Disorders to Homeostasis)

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