scholarly journals Sildenafil Reduces Expression and Release of IL-6 and IL-8 Induced by Reactive Oxygen Species in Systemic Sclerosis Fibroblasts

2020 ◽  
Vol 21 (9) ◽  
pp. 3161 ◽  
Author(s):  
Luigi Di Luigi ◽  
Paolo Sgrò ◽  
Guglielmo Duranti ◽  
Stefania Sabatini ◽  
Daniela Caporossi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Tissue Damage ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Dermal Fibroblasts ◽  
Vascular Damage ◽  
Oxygen Species ◽  
Phosphodiesterase Type 5 Inhibitor

Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud’s Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H2O2), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc.

scholarly journals AB0089 SILDENAFIL COUNTERACTS THE ACTIVATION OF CXCR3/CXCL10, -11 AXIS IN SCLERODERMA FIBROBLASTS EXPOSED TO REACTIVE OXYGEN SPECIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1074.1-1074
Author(s):  
C. Antinozzi ◽  
I. Dimauro ◽  
P. Sgrò ◽  
D. Caporossi ◽  
F. Del Galdo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Reactive Oxygen ◽  
Dermal Fibroblasts ◽  
Vascular Damage ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Luminex Technology

Background:Oxidative stress associated with vascular damage represents one the major contributor in the pathogenesis of systemic sclerosis (SSc) [1]. Indeed, different studies demonstrated that excessive free radicals production can contribute to the activation of fibrotic process in the skin and visceral organs [1]. CXCL10 and CXCL11, together with their receptor CXCR3, are involved in vascular damage and in fibrosis [2]. Furthermore, these chemokines have been proposed as biomarkers of vascular damage progression and severe SSc prognosis [3].Emerging evidences highlight the beneficial effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, to protect different cell types from reactive oxygen species (ROS)-induced DNA damage, in vitro [3]. This effect has been linked to modulation of CXCL10 concentration in different pathological conditions [4,5].Objectives:Here we set out to investigate the effects of sildenafil, in modulating the CXCR3/CXCL10, -11 inflammatory axis in dermal fibroblasts exposed to oxidative stress, in vitro.Methods:Human dermal fibroblasts isolated by SSc skin biopsies were treated for 24h with 100µM of hydrogen peroxide (H2O2), in the presence or not of sildenafil (1µM). Dermal fibrobalsts from healthy skin were used as controls. CXCL10 and CXCL11 were evaluated in cell medium by luminex technology assay; expression of chemokine receptor (CXCR)3 and peroxisome proliferator-activated receptor (PPARγ) (a regulator of CXCL10,-11 mRNA) was evaluated by western blot assay.Results:As showed in figure 1, SSc fibroblasts (grey bar) showed similar basal levels of CXCL10 (A) and CXCL11 (B) to healthy controls (black bar). H2O2 induced a significant increase of both chemokines only in SSc fibroblasts (by 4.6 fold for CXCL10 and by 4.2 fold for CXCL11) (*P<0.05 and **P<0.01 vs. c; #P<0.05 vs. healthy controls). Sildenal pre-incubation reduced by approximatively 50% the effects of H2O2 on chemokines release (Figure 1A and B) (§P<0.05 vs. H2O2), and reduced the expression of CXCR3 and PPARγ induced by hydrogen peroxyde exposure (data not shown).Conclusion:In vitro study on dermal fibroblasts support clinical studies to determine the efficacy of sildenafil in the preventing tissue damage and fibrosis in SSc, by reducing the pro-inflammatory activation induced by oxidative stress.References:[1]Di Luigi L, Sgrò P, Duranti G, Sabatini S, Caporossi D, Del Galdo F, Dimauro I, Antinozzi C. Sildenafil Reduces Expression and Release of IL-6 and IL-8 Induced by Reactive Oxygen Species in Systemic Sclerosis Fibroblasts. Int J Mol Sci. 2020 Apr 30;21(9):3161. doi: 10.3390/ijms21093161. PMID: 32365773; PMCID: PMC7246497.[2]Koper OM, Kamińska J, Sawicki K, Kemona H. CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroinflammation and neurodegeneration. Adv Clin Exp Med. 2018 Jun;27(6):849-856. doi: 10.17219/acem/68846. PMID: 29893515.[3]Crescioli C, Corinaldesi C, Riccieri V, Raparelli V, Vasile M, Del Galdo F, Valesini G, Lenzi A, Basili S, Antinozzi C. Association of circulating CXCL10 and CXCL11 with systemic sclerosis. Ann Rheum Dis. 2018 Dec;77(12):1845-1846. doi: 10.1136/annrheumdis-2018-213257. Epub 2018 May 14. PMID: 29760155; PMCID: PMC6241615.[4]Giannattasio S, Corinaldesi C, Colletti M, Di Luigi L, Antinozzi C, Filardi T, Scolletta S, Basili S, Lenzi A, Morano S, Crescioli C. The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence. J Endocrinol Invest. 2019 Jun;42(6):715-725. doi: 10.1007/s40618-018-0977-y. Epub 2018 Nov 10. PMID: 30415310; PMCID: PMC6531405.[5]You N, Li J, Huang X, Wu K, Tang Y, Wang L, Li H, Mi N, Zheng L. COMMD7 activates CXCL10 production by regulating NF-κB and the production of reactive oxygen species. Mol Med Rep. 2018 May;17(5):6784-6788. doi: 10.3892/mmr.2018.8706. Epub 2018 Mar 8. PMID: 29532873.Disclosure of Interests:None declared

Protection of Human Fibroblasts from Reactive Oxygen Species by Green Tea Polyphenolic Compounds

2005 ◽  
Vol 288-289 ◽  
pp. 665-668 ◽  
Author(s):  
Dong Wook Han ◽  
H.H. Kim ◽  
Hyun Joo Son ◽  
Hyun Sook Baek ◽  
Kwon Yong Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Green Tea ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
High Sensitivity ◽  
Dermal Fibroblasts ◽  
Oxygen Species ◽  
A Cell ◽  
Fcm Analysis

The potential protective roles played by green tea compounds (GTPCs) against reactive oxygen species-induced oxidative stress in cultured fetal human dermal fibroblasts (fHDFs) were investigated according to cell viability measurement methods, such as fluorescence double staining followed by flow cytometry (FCM), MTT assay and crystal violet uptake. Oxidative stress was induced in the fHDFs, either by adding 50 mM H2O2 or by the action of 40 U/L xanthine oxidase (XO) in the presence of xanthine (250 µM). FCM analysis was the most suitable to show that both treatments produced a significant (p < 0.05) reduction in the fHDF viability, attributed to its high sensitivity. On the microscopic observations, the cell death with necrotic morphology was appreciably induced by both treatments. These oxidative stress-induced damages were significantly (p < 0.05) prevented by pre-incubating the fHDFs with 200 µg/ml GTPC for 1 h. These results suggest that GTPC can act as a biological antioxidant in a cell culture experimental model and prevent oxidative stress-induced cytotoxicity in cells.

scholarly journals Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target

2021 ◽  
Vol 10 (20) ◽  
pp. 4791
Author(s):  
Sonsoles Piera-Velazquez ◽  
Sergio A. Jimenez
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Nadph Oxidase ◽  
Therapeutic Target ◽  
Reactive Oxygen ◽  
Dermal Fibroblasts ◽  
Ros Production ◽  
Oxygen Species ◽  
Fibrotic Process

Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise mechanisms mediating oxidative stress development in SSc and its pathogenetic effects have not been fully elucidated. The participation of the NADPH oxidase NOX4, has been suggested and experimentally supported by the demonstration that SSc dermal fibroblasts display constitutively increased NOX4 expression and that reduction or abrogation of NOX4 effects decreased ROS production and the expression of genes encoding fibrotic proteins. Furthermore, NOX4-stimulated ROS production may be involved in the development of certain endothelial and vascular abnormalities and may even participate in the generation of SSc-specific autoantibodies. Collectively, these observations suggest NOX4 as a novel therapeutic target for SSc.

scholarly journals The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 786
Author(s):  
Luigi Di Luigi ◽  
Guglielmo Duranti ◽  
Ambra Antonioni ◽  
Paolo Sgrò ◽  
Roberta Ceci ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Systemic Sclerosis ◽  
Cell Viability ◽  
Redox Homeostasis ◽  
Dermal Fibroblasts ◽  
Oxygen Species ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type ◽  
Oxidative Insult

Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by the increased deposition of extracellular matrix proteins such as collagen and fibronectin. Although the pathogenesis is not completely understood, a number of studies suggest that free radicals could be the major contributors to the disease. Indeed, different studies demonstrated how oxidative stress could contribute to the fibrotic process activation at the level of the skin and visceral organs. Emerging evidences highlight the beneficial effects of sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), which protects different cell lines from the cell damage induced by reactive oxygen species (ROS). These data make sildenafil a good candidate for therapeutic treatment aimed to protect biological macromolecules against oxidative damage, thus preserving cell viability. The purpose of this study was to evaluate the sensitivity of SSc dermal fibroblasts to an oxidative insult and the ability for sildenafil to prevent/reduce the DNA damage due to ROS action. Additionally, we evaluated the capacity for sildenafil to influence redox homeostasis and cytotoxicity, as well as cell proliferation and cell cycle progression. We demonstrated that SSc fibroblasts have an increased sensitivity to a pro-oxidant environment in comparison to healthy controls. The sildenafil treatment reduced ROS-induced DNA damage, counteracted the negative effects of ROS on cell viability and proliferation, and promoted the activity of specific enzymes involved in redox homeostasis maintenance. To our knowledge, in this report, we demonstrate, for the first time, that sildenafil administration prevents ROS-induced instability in human dermal fibroblasts isolated by SSc patients. These results expand the use of PDE5i as therapeutic agents in SSc by indicating a protective role in tissue damage induced by oxidative insult.

scholarly journals The Leaf Extract of Coccinia grandis (L.) Voigt Accelerated In Vitro Wound Healing by Reducing Oxidative Stress Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Poommaree Namchaiw ◽  
Yamaratee Jaisin ◽  
Cholticha Niwaspragrit ◽  
Kittiya Malaniyom ◽  
Anyamanee Auvuchanon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Wound Healing ◽  
Leaf Extract ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Stress Injury ◽  
Ic50 Value

The impairment in the regulation of the physiological process in the inflammatory phase of wound healing results in oxidative stress damage, which increases the severity and extends the healing time. In this study, we aimed to evaluate the radical scavenging properties of Coccinia leaf extract and its ability to ameliorate a migration process in vitro. Coccinia is a medicinal plant that was used in ancient times for relieving insect bite itching and swelling. However, the role of Coccinia leaf extract as an antioxidant related to the process of wound healing has never been studied. In this study, we demonstrated that the leaf extract possessed antioxidant properties that acted as a proton donor to neutralize reactive oxygen species with the IC50 value of 4.85 mg/mL of the extract. It could chelate iron with the IC50 value of 21.39 mg/mL of the extract. The leaf extract protected the human fibroblasts and keratinocytes from hydrogen peroxide-induced oxidative stress by increasing cell survival rate by more than 20% in all test doses. The protective property was dose-dependently correlated with the decrease in reactive oxygen species formation. In addition, the leaf extract enhanced the cell migration rate of fibroblasts and keratinocytes up to 23% compared with vehicle control. The results suggested that Coccinia leaf extract may be a potential herb for increasing the wound healing process with its antioxidant capacity and can be used as an herbal ingredient for the utilization of skincare products.

scholarly journals Obesity, bariatric surgery and oxidative stress

2017 ◽  
Vol 63 (3) ◽  
pp. 229-235 ◽  
Author(s):  
Roberta Cattaneo Horn ◽  
Gabriela Tassotti Gelatti ◽  
Natacha Cossettin Mori ◽  
Ana Caroline Tissiani ◽  
Mariana Spanamberg Mayer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Bariatric Surgery ◽  
Ascorbic Acid ◽  
Body Weight ◽  
Tissue Damage ◽  
Reduced Glutathione ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Obese Women

Summary Introduction: Obesity refers to the accumulation of fatty tissues and it favors the occurrence of oxidative stress. Alternatives that can contribute to body weight reduction have been investigated in order to reduce the production of reactive oxygen species responsible for tissue damage. The aim of the current study was to assess whether the oxidant and antioxidant markers of obese women before and after bariatric surgery were able to reduce oxidative damage. Method: We have assessed 16 morbidly obese women five days before and 180 days after the surgery. The control group comprised 16 non-obese women. Levels of thiobarbituric acid-reactive substances, carbonylated proteins, reduced glutathione and ascorbic acid were assessed in the patients' plasma. Results: Levels of lipid peroxidation and protein carbonylation in the pre-surgical obese women were higher than those of the controls and post-surgical obese women. Levels of reduced glutathione in the pre-surgical obese women were high compared to the controls, and declined after surgery. Levels of ascorbic acid fell in the pre--surgical obese women compared to the control and post-surgical obese women. Conclusion: Body weight influences the production of reactive oxygen species. Bariatric surgery, combined with weight loss and vitamin supplementation, reduces cellular oxidation, thus reducing tissue damage.

scholarly journals Peranan Stres Oksidatif pada Proses Penyembuhan Luka

2018 ◽  
Vol 5 (2) ◽  
pp. 22
Author(s):  
Handy Arief ◽  
M Aris Widodo
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Wound Healing ◽  
Free Radical ◽  
Tissue Damage ◽  
Healing Process ◽  
Reactive Oxygen ◽  
Wound Healing Process ◽  
Oxygen Species

Wound healing is a complex dynamic process characterized by a series of events that occur in almost all type of tissue damage. In the early phase of the inflammatory response, neutrophils and macrophages enters into the injured tissue and the cells produce reactive oxygen species that can give a beneficial or detrimental effects. Oxidative stress is a condition occurs that shows imbalance between prooxidant or free radical and antioxidant that have a function to maintain the condition of the tissue damage that occurs. So Oxidative stress occurs when the production of Reactive Oxygen Species occurring is higher than the antioxidants existing as an intrinsic defense. Reactive Oxygen Species and Reactive Nitrogen Species are important components in the healing process of wounds and is necessary to be in the state of homeostasis to prevent oksidatif stress. The major components of ROS are superoxide (O2•), hydroxyl radical (OH•) and hydrogen peroxide (H2O2), which includes RNS are nitric oxide (NO•), nitrous oxide (NO2•), nitroxyl anion (HNO) and peroxynitrite (ONOO-) which could be form by the reaction between superoxide and nitric oxide. The existence of excessive O2 amount in the wound and the presence of excess NO can increase the incidence of oxidative stress that interfere with wound healing process. Oxidative stress plays a role in the inflammatory phase, proliferation and remodeling phase by increasing angiogenesis and affect other cells including endothelial cells in secreting NO. So the strategy in controlling oxidative stress is by increasing antioxidant level which is a scavenger to free radical excessive superoxide formation so preventing interference with the wound healing process. 

scholarly journals Platelet-derived Growth Factor and Reactive Oxygen Species (ROS) Regulate Ras Protein Levels in Primary Human Fibroblasts via ERK1/2

2005 ◽  
Vol 280 (43) ◽  
pp. 36474-36482 ◽  
Author(s):  
Silvia Svegliati ◽  
Raffaella Cancello ◽  
Paola Sambo ◽  
Michele Luchetti ◽  
Paolo Paroncini ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Platelet Derived Growth Factor ◽  
Oxygen Species ◽  
Ras Protein ◽  
Primary Fibroblasts

The levels of Ras proteins in human primary fibroblasts are regulated by PDGF (platelet-derived growth factor). PDGF induced post-transcriptionally Ha-Ras by stimulating reactive oxygen species (ROS) and ERK1/2. Activation of ERK1/2 and high ROS levels stabilize Ha-Ras protein, by inhibiting proteasomal degradation. We found a remarkable example in vivo of amplification of this circuitry in fibroblasts derived from systemic sclerosis (scleroderma) lesions, producing vast excess of ROS and undergoing rapid senescence. High ROS, Ha-Ras, and active ERK1/2 stimulated collagen synthesis, DNA damage, and accelerated senescence. Conversely ROS or Ras inhibition interrupted the signaling cascade and restored the normal phenotype. We conclude that in primary fibroblasts stabilization of Ras protein by ROS and ERK1/2 amplifies the response of the cells to growth factors and in systemic sclerosis represents a critical factor in the onset and progression of the disease.

scholarly journals Role of Klotho as a Modulator of Oxidative Stress Associated with Ovarian Tissue Cryopreservation

2021 ◽  
Vol 22 (24) ◽  
pp. 13547
Author(s):  
Boram Kim ◽  
Hyunho Yoon ◽  
Tak Kim ◽  
Sanghoon Lee
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Tissue Damage ◽  
Ovarian Tissue ◽  
Reactive Oxygen ◽  
Ovarian Tissue Cryopreservation ◽  
Oxygen Species ◽  
Klotho Protein ◽  
Induced Apoptosis ◽  
Tissue Cryopreservation

Ovarian tissue cryopreservation is the only option for preserving fertility in adult and prepubertal cancer patients who require immediate chemotherapy or do not want ovarian stimulation. However, whether ovarian tissue cryopreservation can ameliorate follicular damage and inhibit the production of reactive oxygen species in cryopreserved ovarian tissue remains unclear. Oxidative stress is caused by several factors, such as UV exposure, obesity, age, oxygen, and cryopreservation, which affect many of the physiological processes involved in reproduction, from maturation to fertilization, embryonic development, and pregnancy. Here, freezing and thawing solutions were pre-treated with N-acetylcysteine (NAC) and klotho protein upon the freezing of ovarian tissue. While both NAC and klotho protein suppressed DNA fragmentation by scavenging reactive oxygen species, NAC induced apoptosis and tissue damage in mouse ovarian tissue. Klotho protein inhibited NAC-induced apoptosis and restored cellular tissue damage, suggesting that klotho protein may be an effective antioxidant for the cryopreservation of ovarian tissue.

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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