Oxidation of Plasmalogens Produces Highly Effective Modulators of Macrophage Function

2000 ◽  
Vol 55 (1-2) ◽  
pp. 115-120 ◽  
Author(s):  
Helmut Heinle ◽  
Nadja Gugeler ◽  
Roswitha Felde ◽  
Dagmar Okech ◽  
Gerhard Spiteller
Keyword(s):  
Degradation Products ◽  
Oxidative Degradation ◽  
Oxidative Modification ◽  
Oxygen Species ◽  
Cytotoxic Effects ◽  
Macrophage Function ◽  
Enhanced Chemiluminescence ◽  
Derivatives Of ◽  
Assay Conditions

Abstract Model derivatives of plasmalogens and chemically synthesized oxidative degradation products as found e.g. during oxidation of low density lipoproteins show strong effects on phagocytosis induced secretion of reactive oxygen species of macrophages which was measured by luminol-enhanced chemiluminescence. Whereas a plasmalogen epoxide showed enhancing effects in submicromolar range, inhibition was found with higher concentrations as well as with a-hydroxyaldehydes. The substances showed only little effects on the non-cellular ROSdependent chemiluminescence of the reaction between hydrogen peroxide and opsonized zymosan and no cytotoxic effects under the assay conditions used. These results show that oxidative modification and degradation of plasmalogens occuring also under pathophysiological situations in vivo produces effective modulators of macrophage function which could be important; e.g. during inflammation or atherogenesis.

Effects of D-Glucose on Chemokinesis and Resting Production of Reactive Oxygen Species in Neutrophil Granulocytes of Lean or Obese-Hyperglycemic Mouse

1997 ◽  
Vol 17 (5) ◽  
pp. 487-498 ◽  
Author(s):  
Per-Arne Oldenborg ◽  
Janove Sehlin
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Neutrophil Function ◽  
Neutrophil Granulocytes ◽  
Oxygen Species ◽  
Enhanced Chemiluminescence ◽  
Chronic Hyperglycemia ◽  
Locomotive Activity

The response to D-glucose (0–21 mM) was studied in neutrophil granulocytes from obese, hyperglycemic and hyperinsulinemic Umeå ob/ob mice and their lean, littermate controls in order to further elucidate the effects of in vivo and in vitro hyperglycemia on neutrophil function. Neutrophil random locomotion on glass and neutrophil resting luminol-enhanced chemiluminescence in cell suspension were studied. Random locomotion was stimulated by D-glucose in neutrophils from both Umeå ob/ob and control mice but the locomotive activity in Umeå ob/ob mouse neutrophils was significantly higher than that found in the controls at 4–21 mM glucose. In both types of mice, the stimulatory effect of D-glucose on random locomotion was diminished at 21 mM glucose (not significantly different from that at 0 mM glucose). Resting chemiluminescence from mouse neutrophils was also stimulated by glucose but here the magnitude of response was similar in neutrophils from both types of mice. These results indicate that chronic hyperglycemia and hyperinsulinemia in the Umeå ob/ob mouse may be associated with an increased neutrophil random locomotive activity but a similar resting production of reactive oxygen species, as compared with neutrophils from control mice at physiological and hyperglycemic glucose concentrations in vitro.

scholarly journals Cytotoxicity of Air Pollutant 9,10-Phenanthrenequinone: Role of Reactive Oxygen Species and Redox Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Manli Yang ◽  
Hassan Ahmed ◽  
Weidong Wu ◽  
Bijie Jiang ◽  
Zhenquan Jia
Keyword(s):  
Reactive Oxygen Species ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Air Pollutant ◽  
Diesel Exhaust Particles ◽  
Political Community ◽  
Oxygen Species ◽  
Cytotoxic Effects

Atmospheric pollution has been a principal topic recently in the scientific and political community due to its role and impact on human and ecological health. 9,10-phenanthrenequinone (9,10-PQ) is a quinone molecule found in air pollution abundantly in the diesel exhaust particles (DEP). This compound has studied extensively and has been shown to develop cytotoxic effects both in vitro and in vivo. 9, 10-PQ has been proposed to play a critical role in the development of cytotoxicity via generation of reactive oxygen species (ROS) through redox cycling. This compound also reduces expression of glutathione (GSH), which is critical in Phase II detoxification reactions. Understanding the underlying cellular mechanisms involved in cytotoxicity can allow for the development of therapeutics designed to target specific molecules significantly involved in the 9,10-PQ-induced ROS toxicity. This review highlights the developments in the understanding of the cytotoxic effects of 9, 10-PQ with special emphasis on the possible mechanisms involved.

scholarly journals Antimalarial Properties of Dunnione Derivatives as NQO2 Substrates

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3697 ◽  
Author(s):  
Monivan Chhour ◽  
Agnès Aubouy ◽  
Sandra Bourgeade-Delmas ◽  
Pierre Pério ◽  
Hélène Ternet-Fontebasso ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Natural Product ◽  
Murine Model ◽  
Blood Cells ◽  
Oxygen Species ◽  
Ic50 Value ◽  
Quinone Reductases ◽  
Derivatives Of

Dunnione, a natural product isolated from the leaves of Streptocarpus dunnii (Gesneriaceae), acts as a substrate for quinone-reductases that may be associated with its antimalarial properties. Following our exploration of reactive oxygen species-producing compounds such as indolones, as possible new approaches for the research of new ways to treat this parasitosis, we explored derivatives of this natural product and their possible antiplasmodial and antimalarial properties, in vitro and in vivo, respectively. Apart from one compound, all the products tested had weak to moderate antiplasmodial activities, the best IC50 value being equal to 0.58 µM. In vivo activities in the murine model were moderate (at a dose of 50 mg/kg/mice, five times higher than the dose of chloroquine). These results encourage further pharmacomodulation steps to improve the targeting of the parasitized red blood cells and antimalarial activities.

scholarly journals Characteristic synergistic cytotoxic effects toward cells in graphene oxide dressing with cadmium and copper ions

2019 ◽  
Vol 8 (6) ◽  
pp. 908-917 ◽  
Author(s):  
Yiyang Dong ◽  
Yulin Chang ◽  
Haidi Gao ◽  
Victoria Arantza León Anchustegui ◽  
Qiang Yu ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Copper Ions ◽  
Membrane Integrity ◽  
In Vitro Toxicity ◽  
Oxygen Species ◽  
Human Beings ◽  
Cell Toxicity ◽  
Cytotoxic Effects

Abstract The increasing applications of graphene oxide (GO) in bio-medicine, environment and other fields enhance the exposure possibility of human beings to GO. Studies have been performed to address the in vitro toxicity of GO; however, little information on the in vivo biological consequence of GO with other common disasters is available, especially when cells are co-exposed to GO and common metal ions. To explore the influence and possible mechanisms of such co-exposure scenarios, a series of tests of cell viability, membrane integrity, reactive oxygen species (ROS), cell morphology, and Cd2+ distribution, were conducted. The results showed that the synergistic toxic mechanisms of GO and Cd2+, initiated from the adhesion of GO on HeLa cells, and followed by the recruitment of Cd2+ ions around the cell membrane, impaired the membrane integrity, morphology and adhesion capability, and triggered cell toxicity. The synergistic toxic mechanism of GO and Cu2+ mainly correlated to ROS, while no obvious relationship with membrane integrity was observed. The findings are envisaged to facilitate the application of GO in biology and related fields.

scholarly journals In vitro effect of N-acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites

2013 ◽  
Vol 33 (1) ◽  
pp. 41-53 ◽  
Author(s):  
J J van Tonder ◽  
M Gulumian ◽  
A D Cromarty ◽  
V Steenkamp
Keyword(s):  
Apoptotic Cell ◽  
Ros Generation ◽  
Oxygen Species ◽  
Cellular Viability ◽  
Cytotoxic Effects ◽  
Hepatocyte Injury ◽  
Intracellular Changes ◽  
Vitro Effect

The organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT), is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo. N-Acetylcysteine (NAC) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds. The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites, dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane. HepG2 cell cultures were used to assess the following parameters of toxicity: cellular viability, intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential and initiation of apoptosis. None of the three test compounds induced ROS generation, yet exposure to any of the three compounds produced mitochondrial hyperpolarization, which was countered by NAC pretreatment. All three test compounds also induced apoptotic cell death, which was inhibited by NAC. Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure, it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations. As the same outcome may also occur in vivo, results from the present study raise concern about the use of NAC as treatment for DDT-induced hepatotoxicity.

In vitro cytocompatibility testing of oxidative degradation products

2021 ◽  
pp. 088391152110031
Author(s):  
Scott M Herting ◽  
Mary Beth B Monroe ◽  
Andrew C Weems ◽  
Sam T Briggs ◽  
Grace K Fletcher ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Culture ◽  
Culture Media ◽  
Degradation Products ◽  
Oxidative Degradation ◽  
Cell Culture Media ◽  
Novel Approach ◽  
Gene And Protein Expression

Implantable medical devices must undergo thorough evaluation to ensure safety and efficacy before use in humans. If a device is designed to degrade, it is critical to understand the rate of degradation and the degradation products that will be released. Oxidative degradation is typically modeled in vitro by immersing materials or devices in hydrogen peroxide, which can limit further analysis of degradation products in many cases. Here we demonstrate a novel approach for testing the cytocompatibility of degradation products for oxidatively-degradable biomaterials where the materials are exposed to hydrogen peroxide, and then catalase enzyme is used to convert the hydrogen peroxide to water and oxygen so that the resulting aqueous solution can be added to cell culture media. To validate our results, expected degradation products are also synthesized then added to cell culture media. We used these methods to evaluate the cytocompatibility of degradation products from an oxidatively-degradable shape memory polyurethane designed in our lab and found that the degradation of these polymers is unlikely to cause a cytotoxic response in vivo based on the guidance provided by ISO 10993-5. These methods may also be applicable to other biocompatibility tests such as tests for mutagenicity or systemic toxicity, and evaluations of cell proliferation, migration, or gene and protein expression.

Superoxide stimulates NaCl absorption by the thick ascending limb

2002 ◽  
Vol 283 (5) ◽  
pp. F957-F962 ◽  
Author(s):  
Pablo A. Ortiz ◽  
Jeffrey L. Garvin
Keyword(s):  
Xanthine Oxidase ◽  
In Vivo Studies ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Cytotoxic Effects ◽  
Nacl Absorption ◽  
Enhanced Chemiluminescence ◽  
Sprague Dawley Rats

The thick ascending limb of the loop of Henle (THAL) plays an important role in the regulation of NaCl and water reabsorption. In vivo studies have shown that the free radical superoxide (O[Formula: see text]) stimulates Na and water reabsorption by the kidney. However, it is not known whether O[Formula: see text]regulates transport along the nephron in general or in the THAL specifically. We hypothesized that O[Formula: see text] stimulates THAL NaCl reabsorption. Cl absorption was measured in isolated, perfused THALs from Sprague-Dawley rats. First, we tested whether extracellular O[Formula: see text] stimulates Cl absorption. Addition of the O[Formula: see text]-generating system xanthine oxidase/hypoxanthine increased Cl absorption from 112.7 ± 12.0 to 146.2 ± 13.9 pmol · mm−1· min−1, a 33% increase ( P < 0.03). When superoxide dismutase (300 U/ml) was present in the bath, addition of xanthine oxidase/hypoxanthine did not significantly increase Cl absorption (116.9 ± 13.8 vs. 102.5 ± 8.5 pmol · mm−1· min−1). Furthermore, adding 200 nM H2O2to the bath did not significantly affect Cl absorption (from 130.3 ± 13.7 to 125.3 ± 19.6 pmol · mm−1· min−1). Because extracellular O[Formula: see text] stimulated Cl absorption, we next tested whether endogenously produced O[Formula: see text] could stimulate transport. Under basal conditions, THALs produced detectable amounts of O[Formula: see text], as measured by lucigenin-enhanced chemiluminescence. Adding the O[Formula: see text] scavenger tempol to the bath decreased Cl absorption from 198.1 ± 35.4 to 132.4 ± 23.5 pmol · mm−1· min−1, a 31% decrease ( P < 0.02). To make sure tempol was not exerting cytotoxic effects, we tested whether its effect was reversible. With tempol in the bath, Cl absorption was 117.2 ± 9.3 pmol · mm−1· min−1. Sixty minutes after tempol was removed from the bath, Cl absorption had increased to 149.2 ± 9.1 pmol · mm−1· min−1( P < 0.05). We concluded that both exogenous and endogenous O[Formula: see text] stimulate THAL NaCl absorption. To our knowledge, these are the first data showing a direct effect of O[Formula: see text] on nephron transport.

Silica Gel-mediated Oxidation of Prenyl Motifs Generates Natural Product-Like Artifacts

Planta Medica ◽  
2021 ◽  
Author(s):  
Yu Tang ◽  
J. Brent Friesen ◽  
Dejan S. Nikolić ◽  
David C. Lankin ◽  
James B. McAlpine ◽  
...  
Keyword(s):  
Silica Gel ◽  
Degradation Product ◽  
Degradation Products ◽  
Chemical Shifts ◽  
Oxidative Degradation ◽  
Coupling Constants ◽  
Metabolite Formation ◽  
Olefinic Bond ◽  
The Impact

AbstractPrenyl moieties are commonly encountered in the natural products of terpenoid and mixed biosynthetic origin. The reactivity of unsaturated prenyl motifs is less recognized and shown here to affect the acyclic Rhodiola rosea monoterpene glycoside, kenposide A (8), which oxidizes readily on silica gel when exposed to air. The major degradation product mediated under these conditions was a new aldehyde, 9. Exhibiting a shortened carbon skeleton formed through the breakdown of the terminal isopropenyl group, 9 is prone to acetalization in protic solvents. Further investigation of minor degradation products of both 8 and 8-prenylapigenin (8-PA, 12), a flavonoid with an ortho-prenyl substituent, revealed that the aldehyde formation was likely realized through epoxidation and subsequent cleavage at the prenyl olefinic bond. Employment of 1H NMR full spin analysis (HiFSA) achieved the assignment of all chemical shifts and coupling constants of the investigated terpenoids and facilitated the structural validation of the degradation product, 9. This study indicates that prenylated compounds are generally susceptible to oxidative degradation, particularly in the presence of catalytic mediators, but also under physiological conditions. Such oxidative artifact/metabolite formation leads to a series of compounds with prenyl-derived (cyclic) partial structures that are analogous to species formed during Phase I metabolism in vivo. Phytochemical and pharmacological studies should take precautions or at least consider the impact of (unavoidable) exposure of prenyl-containing compounds to catalytic and/or oxidative conditions.

scholarly journals Chemical Basis of Reactive Oxygen Species Reactivity and Involvement in Neurodegenerative Diseases

2019 ◽  
Vol 20 (10) ◽  
pp. 2407 ◽  
Author(s):  
Fabrice Collin
Keyword(s):  
Reactive Oxygen Species ◽  
Neurodegenerative Diseases ◽  
Fatty Acid Content ◽  
Oxidative Degradation ◽  
Chemical Properties ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Intrinsic Nature ◽  
Metabolism Regulation

Increasing numbers of individuals suffer from neurodegenerative diseases, which are characterized by progressive loss of neurons. Oxidative stress, in particular, the overproduction of Reactive Oxygen Species (ROS), play an important role in the development of these diseases, as evidenced by the detection of products of lipid, protein and DNA oxidation in vivo. Even if they participate in cell signaling and metabolism regulation, ROS are also formidable weapons against most of the biological materials because of their intrinsic nature. By nature too, neurons are particularly sensitive to oxidation because of their high polyunsaturated fatty acid content, weak antioxidant defense and high oxygen consumption. Thus, the overproduction of ROS in neurons appears as particularly deleterious and the mechanisms involved in oxidative degradation of biomolecules are numerous and complexes. This review highlights the production and regulation of ROS, their chemical properties, both from kinetic and thermodynamic points of view, the links between them, and their implication in neurodegenerative diseases.

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