Beneficial effects of nontoxic ozone on H2O2-induced stress and inflammation

2016 ◽  
Vol 94 (6) ◽  
pp. 577-583 ◽  
Author(s):  
Altug Kucukgul ◽  
Suat Erdogan ◽  
Ramazan Gonenci ◽  
Gonca Ozan

In this study, the anti-oxidant and anti-inflammatory efficacy of ozone oxidative preconditioning (OOP) were investigated on hydrogen peroxide (H2O2)-induced human lung alveolar cells. In MTT and trypan blue viability tests, while 100 μmol/L H2O2caused a 17.3% and 21.9% decrease in the number of living cells, respectively, ozone at 20 μmol/L regenerated cell proliferation and prevented 9.6% and 11.0% of cell loss, respectively. In addition, H2O2decreased the transcription levels of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) 5.43-, 2.89-, and 5.33-fold, respectively, while it increased Bax, NF-κβ, TNF-α, and iNOS expression 1.57-, 1.32-, 1.40-, and 1.41-fold, respectively. Ozone pretreatment, however, increased CAT, GPx, and SOD transcription levels 7.08-, 5.17-, and 6.49-fold and decreased Bax, NF-κβ, TNF-α, and iNOS transcriptions by 1.25-, 0.76-, 3.63-, and 7.91-fold, respectively. Moreover, intracellular glutathione (GSH) level and SOD activity were decreased by 46.2% and 45.0% in the H2O2treatment group, and OOP recovered 58.5% and 20.1% of the decreases caused by H2O2. H2O2also increased nitrite levels 7.84-fold, and OOP reduced this increase by half. Consequently, OOP demonstrated potent anti-oxidant and anti-inflammatory effects on in vitro model of oxidative stress-induced lung injury.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.


2018 ◽  
Vol 19 (11) ◽  
pp. 3602 ◽  
Author(s):  
Jae Lee ◽  
Hyunwoong Lim ◽  
Jae Ahn ◽  
Dongsik Jang ◽  
Seung Lee ◽  
...  

In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. The BMP-2/TA/PCL scaffold showed controlled and sustained BMP-2 release. It effectively scavenged reactive oxygen species (ROS) in cells, and increased the proliferation of MC3T3-E1 cells pre-treated with hydrogen peroxide (H2O2). Additionally, the BMP-2/TA/PCL scaffold significantly suppressed the mRNA levels of pro-inflammatory cytokines, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-induced MC3T3-E1 cells. Furthermore, it showed outstanding enhancement of the osteogenic activity of MC3T3-E1 cells through increased alkaline phosphatase (ALP) activity and calcium deposition. Our findings demonstrated that the BMP-2/TA/PCL scaffold plays an important role in scavenging ROS, suppressing inflammatory response, and enhancing the osteogenic differentiation of cells.


Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 825
Author(s):  
Mohammad Khalid ◽  
Mohammed H. Alqarni ◽  
Ambreen Shoaib ◽  
Muhammad Arif ◽  
Ahmed I. Foudah ◽  
...  

The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract’s ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Katharina Mörs ◽  
Ramona Sturm ◽  
Jason-Alexander Hörauf ◽  
Shinwan Kany ◽  
Paola Cavalli ◽  
...  

Background. In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation. Methods. HepG2 cells were stimulated with IL-1β and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF-α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed. Results. In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1β-induced IL-6 and TNF-α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1β stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1β-induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation. Conclusion. EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.


2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110325
Author(s):  
Miao Yu ◽  
Long Sun ◽  
Pengfei Ba ◽  
Linxia Li ◽  
Jing Chen ◽  
...  

Objective The growth factor progranulin (PGRN) is widely expressed and plays important roles in anti-inflammatory signaling and bone regeneration. However, the anti-inflammatory and pro-osteogenic roles of PGRN in periodontitis are seldom studied. We used an in vitro model to investigate whether PGRN can promote osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Methods PDLSCs were treated with PGRN (0 to 100 ng/mL) and the optimal concentrations required to induce proliferation and osteogenesis were identified. PDLSCs were cultured with 10 ng/mL tumor necrosis factor (TNF)-α, 25 ng/mL PGRN, or 10 ng/mL TNF-α + 25 ng/ml PGRN; untreated PDLSCs were used as controls. The effects of PGRN on PDLSC proliferation and osteogenic differentiation were assessed. Results PGRN (5, 25, and 50 ng/mL) promoted PDLSC proliferation and osteogenic differentiation, with the 25-ng/mL dose showing the largest effect. Furthermore, 25 ng/mL PGRN reversed inhibition of osteogenic differentiation by TNF-α. Conclusion PGRN promotes PDLSC proliferation, osteogenic differentiation, and mineralization in both inflammatory and non-inflammatory conditions. The 25-ng/mL PRGN dose was the most suitable for inducing proliferation and osteogenesis. Further studies using animal models will be required to obtain pre-clinical evidence to support using PGRN as a treatment for periodontitis.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3212 ◽  
Author(s):  
Raffaela Fuccelli ◽  
Roberto Fabiani ◽  
Patrizia Rosignoli

Hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), the major phenol derived from olive oil consumption, has shown different anti-inflammatory and anti-oxidant activities in vitro which may explain the chronic-degenerative diseases preventive properties of olive oil. The aim of this study was to examine the ability of HT reduce inflammatory markers, Cyclooxygenase-2 (COX2) and Tumour Necrosis Factor alfa (TNF-α and oxidative stress in vivo on a mouse model of systemic inflammation. Balb/c mice were pre-treated with HT (40 and 80 mg/Kg b.w.) and then stimulated by intraperitoneal injection of lipopolysaccharide (LPS). Blood was collected to measure COX2 gene expression by qPCR and TNF-α level by ELISA kit in plasma. In addition, the total anti-oxidant power of plasma and the DNA damage were measured by FRAP test and COMET assay, respectively. LPS increased the COX2 expression, the TNF-α production and the DNA damage. HT administration prevented all LPS-induced effects and improved the anti-oxidant power of plasma. HT demonstrated in vivo anti-inflammatory and anti-oxidant abilities. The results may explain the health effects of olive oil in Mediterranean diet. HT represents an interesting molecule for the development of new nutraceuticals and functional food useful in chronic diseases prevention.


2011 ◽  
Vol 106 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Giuliana Trefiletti ◽  
Anna Rita Togna ◽  
Valentina Latina ◽  
Carolina Marra ◽  
Marcella Guiso ◽  
...  

Extra-virgin olive oil is an integral ingredient of the Mediterranean diet, and it has been suggested that its high consumption has beneficial effects on human health. Its protective effect, in particular against the development of CVD, has been related not only to the high content of oleic acid, but also to the antioxidant and anti-inflammatory properties of polyphenols. In order to verify the anti-inflammatory and anti-atherogenic properties of hydroxy-isochromans, a class of ortho-diphenols present in extra-virgin olive oil, we investigated the potential ability of 1-phenyl-6,7-dihydroxy-isochroman (L137) to modulate the production of key inflammatory mediators by human monocytes, by evaluating its in vitro effects on prostanoid (thromboxane A2 and PGE2) and cytokine (TNF-α) production. Its effect on the protein expression of the inducible form of cyclo-oxygenase-2 (COX-2), a pro-inflammatory enzyme responsible for elevated prostanoid levels, was also explored. The results showed that L137 significantly inhibited both prostanoid and TNF-α production in lipopolysaccharide-primed human monocytes in a dose-dependent manner, by inhibiting the COX activity of COX-2. We also demonstrated that the effects of the isochroman are mediated, at least partly, through the suppression of NF-κB activation leading to the down-regulation of the synthesis of COX-2.


Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.


1984 ◽  
Vol 51 (01) ◽  
pp. 089-092 ◽  
Author(s):  
M A Boogaerts ◽  
J Van de Broeck ◽  
H Deckmyn ◽  
C Roelant ◽  
J Vermylen ◽  
...  

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.


Author(s):  
Thea Magrone ◽  
Emilio Jirillo ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Paolo Romita ◽  
...  

Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Method: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded. Result: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.


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