scholarly journals Synthesis, Structure and Impact of 5-Aminoorotic Acid and Its Complexes with Lanthanum(III) and Gallium(III) on the Activity of Xanthine Oxidase

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4503
Author(s):  
Lozan Todorov ◽  
Luciano Saso ◽  
Khedidja Benarous ◽  
Maria Traykova ◽  
Abderahmane Linani ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Chemical Structure ◽  
Superoxide Radical ◽  
Coordination Complexes ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anticancer Properties ◽  
Physiological Processes ◽  
Potassium Superoxide ◽  
Modern Methods

The superoxide radical ion is involved in numerous physiological processes, associated with both health and pathology. Its participation in cancer onset and progression is well documented. Lanthanum(III) and gallium(III) are cations that are known to possess anticancer properties. Their coordination complexes are being investigated by the scientific community in the search for novel oncological disease remedies. Their complexes with 5-aminoorotic acid suppress superoxide, derived enzymatically from xanthine/xanthine oxidase (X/XO). It seems that they, to differing extents, impact the enzyme, or the substrate, or both. The present study closely examines their chemical structure by way of modern methods—IR, Raman, and 1H NMR spectroscopy. Their superoxide-scavenging behavior in the presence of a non-enzymatic source (potassium superoxide) is compared to that in the presence of an enzymatic source (X/XO). Enzymatic activity of XO, defined in terms of the production of uric acid, seems to be impacted by both complexes and the pure ligand in a concentration-dependent manner. In order to better relate the compounds’ chemical characteristics to XO inhibition, they were docked in silico to XO. A molecular docking assay provided further proof that 5-aminoorotic acid and its complexes with lanthanum(III) and gallium(III) very probably suppress superoxide production via XO inhibition.

scholarly journals Radical scavenging activity of crude polysaccharides from Camellia sinensis

2011 ◽  
Vol 63 (3) ◽  
pp. 717-721
Author(s):  
Fan Yang ◽  
Zhiwei Yang ◽  
Jianbo Xiao
Keyword(s):  
Molecular Weight ◽  
Free Radical ◽  
Camellia Sinensis ◽  
Superoxide Radical ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Dependent Manner ◽  
Scavenging Activity ◽  
Concentration Dependent Manner ◽  
Molecular Weights

A preparation of crude polysaccharides (TPS) was isolated from Camellia sinensis by precipitation and ultrafiltration. TPS1, TPS2, and TPS3 had molecular weights of 240, 21.4, and 2.46 kDa, respectively. The radical scavenging activities of TPS were evaluated by DPPH free radical, hydroxyl radical and superoxide radical scavenging. These results revealed that TPS exhibited strong radical scavenging activity in a concentration-dependent manner. TPS3 with lowest molecular weight showed a higher radical scavenging activity.

scholarly journals Interaction Of Propylthiouracil With Model Systems Generating A Superoxide Radical

2014 ◽  
Vol 7 (2) ◽  
pp. 93-98
Author(s):  
Maria L. Valcheva-Traykova ◽  
Trayko T. Traykov ◽  
Georgeta S. Bocheva
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Tissue Damage ◽  
Superoxide Radical ◽  
Model Systems ◽  
Prooxidant Effect ◽  
System A ◽  
Potassium Superoxide

SummaryPropylthiouracil is used against Grave's Disease and for developing animal models of hypothyroidism. Apart from depressed metabolism, free radical-induced tissue damage has been registered as an effect from this drug. Superoxide is essential for generation of free radicals in tissues. The mutual effects of Propylthiouracil and superoxide radical have not been well investigated.Thein vitroeffects of Propylthiouracil on the free radicals in three model systems generating superoxide were measured using luminol-dependent chemiluminescence and spectrophotometry. The drug did not affect the formation of free radicals in the presence of potassium superoxide and in pyrogallol-oxygen solutions, while in the presence of the xanthine/xanthine oxidase system a distinct prooxidant effect was registered. The investigation of the system propylthiouracil/xanthine oxidase showed mild free radicals formation along with decreasing intensities of the drug's UV-specter.Ourin vitroinvestigation indicated that, along with the transformation of xanthine to uric acid over xanthine oxidase, some free radicals may be produced due to the interaction of propylthiouracil with the enzyme. It was proposed that this might contribute to thein vivofree radicals-induced tissue damage observed in the presence of propylthiouracil.

scholarly journals 20-HETE increases superoxide production and activates NAPDH oxidase in pulmonary artery endothelial cells

2008 ◽  
Vol 294 (5) ◽  
pp. L902-L911 ◽  
Author(s):  
Meetha Medhora ◽  
Yuenmu Chen ◽  
Stephanie Gruenloh ◽  
Daniel Harland ◽  
Sreedhar Bodiga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Nadph Oxidase ◽  
Oxidation Products ◽  
Dependent Manner ◽  
Ros Production ◽  
Concentration Dependent Manner ◽  
Physiological Processes ◽  
Contraction And Relaxation ◽  
Endothelial Nitric Oxide

Reactive oxygen species (ROS) signal vital physiological processes including cell growth, angiogenesis, contraction, and relaxation of vascular smooth muscle. Because cytochrome P-450 family 4 (CYP4)/20-hydroxyeicosatetraenoic acid (20-HETE) has been reported to enhance angiogenesis, pulmonary vascular tone, and endothelial nitric oxide synthase function, we explored the potential of this system to stimulate bovine pulmonary artery endothelial cell (BPAEC) ROS production. Our data are the first to demonstrate that 20-HETE increases ROS in BPAECs in a time- and concentration-dependent manner as detected by enhanced fluorescence of oxidation products of dihydroethidium (DHE) and dichlorofluorescein diacetate. An analog of 20-HETE elicits no increase in ROS and blocks 20-HETE-evoked increments in DHE fluorescence, supporting its function as an antagonist. Endothelial cells derived from bovine aortas exhibit enhanced ROS production to 20-HETE quantitatively similar to that of BPAECs. 20-HETE-induced ROS production in BPAECs is blunted by pretreatment with polyethylene-glycolated SOD, apocynin, inhibition of Rac1, and a peptide-based inhibitor of NADPH oxidase subunit p47phox association with gp91. These data support 20-HETE-stimulated, NADPH oxidase-derived, and Rac1/2-dependent ROS production in BPAECs. 20-HETE promotes translocation of p47phox and tyrosine phosphorylation of p47phox in a time-dependent manner as well as increased activated Rac1/2, providing at least three mechanisms through which 20-HETE activates NADPH oxidase. These observations suggest that 20-HETE stimulates ROS production in BPAECs at least in part through activation of NADPH oxidase within minutes of application of the lipid.

scholarly journals Artemisinin Inhibits the Migration and Invasion in Uveal Melanoma via Inhibition of the PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Mohd Farhan ◽  
Marta Silva ◽  
Xing Xingan ◽  
Zhiwei Zhou ◽  
Wenhua Zheng
Keyword(s):  
Uveal Melanoma ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Anticancer Effect ◽  
Concentration Dependent Manner ◽  
Ocular Tissues ◽  
Anticancer Properties ◽  
Mitochondrial Membrane Potential Loss

Uveal melanoma is the most common primary ocular neoplasm in adults, with many patients ending up developing liver metastasis and facing a significant reduction of their life expectancy due to the lack of efficient treatments. Artemisinin is an antimalarial drug that has been widely used in the clinic and whose anticancer properties have also been described. Its reported safety, affordability, and ability to reach the ocular tissues point that it has a potential therapeutic agent against uveal melanoma. In the present study, we found that a subantimalaria dosage of artemisinin significantly attenuated the migration and invasion potential of uveal melanoma cells, in a concentration-dependent manner. Assessment of the mechanisms underlying artemisinin anticancer action revealed that its use dramatically reduced the phosphorylation of PI3K, AKT, and mTOR in UM cells. Further inhibition of PI3K signaling, using LY294002, or of mTOR, by rapamycin, blocked the migration and invasion of UM cells similarly to artemisinin. In contrast, AKT or mTOR activator (Sc79 and MHY1485, respectively) attenuated the inhibitory effect of artemisinin on the migration and invasion abilities of UM cells, further validating that artemisinin’s anticancer effect is likely to be mediated via inhibition of the PI3K/AKT/mTOR pathway. Artemisinin also induced mitochondrial membrane potential loss and apoptosis of UM cells, having no significant toxic effect on normal retinal neuronal cells RGC-5 and epithelial cells D407. These findings and the reported safety of artemisinin’s clinical dosage strongly suggest the therapeutic potential of artemisinin in the prevention and treatment of uveal melanomas.

Determination of the Excitatory Potencies of Fluoroquinolones in the Central Nervous System by an In Vitro Model

1998 ◽  
Vol 42 (7) ◽  
pp. 1831-1836 ◽  
Author(s):  
Gabriele Schmuck ◽  
Anja Schürmann ◽  
Gerhard Schlüter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chemical Structure ◽  
Rank Order ◽  
Dose Range ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Hippocampus Slice

ABSTRACT Fluoroquinolones have been reported to induce central nervous system side effects, including seizures and psychiatric events. Although relatively rare in patients up to now, the proconvulsant activity depends on the chemical structure and might be a critical endpoint of some new representatives of this valuable class of antimicrobials. The electrophysiological determination of field potentials in the CA1 region of the rat hippocampus slice allowed an assessment of the excitatory potential of fluoroquinolones and might be predictive for their neurotoxic potency in vivo. An optimization of this method and its extension to other fluoroquinolones resulted in a defined rank order. Well-known already-marketed quinolones as well as some fluoroquinolones under evaluation and development were used. The dose range tested was between 0.5 and 4 μmol/liter, which was comparable to the therapeutic concentration in the brain. All tested compounds increased the population spike amplitude in a concentration-dependent manner, and the resulting excitatory potency was highly dependent on the chemical structure, with compounds ranging from least to most excitatory as follows: ofloxacin, ciprofloxacin, nalidixic acid, moxifloxacin (= BAY × 8843), fleroxacin, lomefloxacin, enoxacin, clinafloxacin (much more excitatory than enoxacin), tosufloxacin, trovafloxacin, BAY 15-7828, and BAY × 9181 (much more excitatory than BAY 15-7828). The proposed hippocampus slice model not only is suitable for giving valuable alerts as to convulsive potential during candidate selection but also enables mechanistic investigations. These investigations pointed to theN-methyl-d-aspartate receptor as the probable target of the fluoroquinolone effects.

Protective Effects of Indonesian Propolis Against Light-Induced Retinal Damage

2017 ◽  
Vol 9 (02) ◽  
Author(s):  
Paula M. Kustiawan ◽  
Hiroyuki Okuyoshi ◽  
Yoshiki Kuse ◽  
Hiroshi Izawa ◽  
Yuichi Saito ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Caspase 3 ◽  
Biological Activities ◽  
Outer Nuclear Layer ◽  
Stingless Bee ◽  
Light Irradiation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Anticancer Properties

The pharmacological and biological activities of Indonesian propolis are mostly unexplored except for its anticancer properties. This study was designed to explore the protective effects of the methanol extract of Indonesian propolis (MEP) obtained from the stingless bee (Trigona incisa) against light-induced retinal photoreceptor damage. Murine photoreceptor (661W) cells were cultured and treated with MEP. The cells were exposed to cellular stress inducers such as tunicamycin, hydrogen peroxide, and light irradiation. The protective effects of MEP were assessed by determining production of intracellular reactive oxygen species (ROS), analyzing changes in nuclear factor-kappa B (NF-κB) level, analyzing caspase-3/7 activation, and by using the zebrafish retinal degeneration model. MEP significantly reduced cell death induced by tunicamycin, hydrogen peroxide, and white light irradiation in a concentration-dependent manner. The phosphorylation of NF-κB decreased and light-induced activation of caspase-3/7 and intracellular accumulation of ROS were inhibited. The thickness of outer nuclear layer (ONL) in zebrafish retina significantly increased following MEP treatment. The MEP obtained from stingless bee propolis has a protective effect on photoreceptor retinal cells and has the potential to be developed as a supplement in prevention of retinal diseases.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

Trimucytin: A Collagen-Like Aggregating Inducer Isolated from Trimeresurus mucrosquamatus Snake Venom

1993 ◽  
Vol 69 (03) ◽  
pp. 286-292 ◽  
Author(s):  
Che-Ming Teng ◽  
Feng-Nien Ko ◽  
Inn-Ho Tsai ◽  
Man-Ling Hung ◽  
Tur-Fu Huang
Keyword(s):  
Platelet Aggregation ◽  
Snake Venom ◽  
Inositol Phosphate ◽  
Shape Change ◽  
Platelet Activating Factor ◽  
Atp Release ◽  
Platelet Membrane ◽  
Thromboxane B2 ◽  
Dependent Manner ◽  
Concentration Dependent Manner

SummaryTrimucytin is a potent platelet aggregation inducer isolated from Trimeresurus mucrosquamatus snake venom. Similar to collagen, trimucytin has a run of (Gly-Pro-X) repeats at the N-terminal amino acids sequence. It induced platelet aggregation, ATP release and thromboxane formation in rabbit platelets in a concentration-dependent manner. The aggregation was not due to released ADP since it was not suppressed by creatine phosphate/creatine phosphokinase. It was not either due to thromboxane A2 formation because indomethacin and BW755C did not have any effect on the aggregation even thromboxane B2 formation was completely abolished by indomethacin. Platelet-activating factor (PAF) was not involved in the aggregation since a PAF antagonist, kadsurenone, did not affect. However, RGD-containing peptide triflavin inhibited the aggregation, but not the release of ATP, of platelets induced by trimucytin. Indomethacin, mepacrine, prostaglandin E1 and tetracaine inhibited the thromboxane B2 formation of platelets caused by collagen and trimucytin. Forskolin and sodium nitroprusside inhibited both platelet aggregation and ATP release, but not the shape change induced by trimucytin. In quin-2 loaded platelets, the rise of intracellular calcium concentration caused by trimucytin was decreased by 12-O-tetradecanoyl phorbol-13 acetate, imipramine, TMB-8 and indomethacin. In the absence of extracellular calcium, both collagen and trimucytin caused no thromboxane B2 formation, but still induced ATP release which was completely blocked by R 59022. Inositol phosphate formation in platelets was markedly enhanced by trimucytin and collagen. MAB1988, an antibody against platelet membrane glycoprotein Ia, inhibited trimucytinand collagen-induced platelet aggregation and ATP release. However, trimucytin did not replace the binding of 125I-labeled MAB1988 to platelets. Platelets pre-exposed to trimucytin were resistant to the second challenge with trimucytin itself or collagen. It is concluded that trimucytin may activate collagen receptors on platelet membrane, and cause aggregation and release mainly through phospholipase C-phosphoinositide pathway.

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