Redox Properties of Novel Antioxidant 5,8-Dihydroxycoumarin: Implications for its Prooxidant Cytotoxicity

2005 ◽  
Vol 60 (11-12) ◽  
pp. 849-854 ◽  
Author(s):  
Aušra Nemeikaitė-Čėnienė ◽  
Audronė Marozienė ◽  
Audrius Pukalskas ◽  
Petras Rimantas Venskutonis ◽  
Narimantas Čėnasb
Keyword(s):  
Reduced Glutathione ◽  
Leukemia Virus ◽  
Redox Properties ◽  
Cytotoxic Action ◽  
Hydrogen Electrode ◽  
Midpoint Potential ◽  
Normal Hydrogen ◽  
Hierochloe Odorata ◽  
Dt Diaphorase ◽  
Cytochrome P 450

The aim of this work was to characterize the redox properties of the new antioxidant 5,8- dihydroxycoumarin (5,8-DHC), isolated from sweet grass (Hierochloë odorata L.), and to determine its impact on its cytotoxic action. Reversible electrochemical oxidation of 5,8- DHC at pH 7.0 was characterized by the midpoint potential (Ep/2) of 0.23 V vs. the normal hydrogen electrode. 5,8-DHC was slowly autoxidized at pH 7.0, and it was active as a substrate for peroxidase (POD, EC 1.11.1.7) and tyrosinase (TYR, EC 1.14.18.1). Oxidation of 5,8-DHC by POD/H2O2 yielded the product(s) which reacted with reduced glutathione and supported the oxidation of NADPH by ferredoxin:NADP+ reductase (FNR, EC 1.18.1.2) and NAD(P)H:quinone oxidoreductase (NQO1, DT-diaphorase, EC 1.6.99.2). The concentration of 5,8-DHC for 50% survival of bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) during a 24-h incubation was (60 ± 5.5) μm. Cytotoxicity of 5,8-DHC was decreased by desferrioxamine, catalase, the antioxidant N,N’-diphenyl-p-phenylene diamine, and potentiated by 1,3-bis-(2-chloroethyl)-1-nitrosourea and dicumarol, an inhibitor of NQO1. This shows that 5,8-DHC possesses the oxidative stress-type cytotoxicity, evidently due to the action of quinodal oxidation product(s). The protective effect of isoniazide, an inhibitor of cytochrome P-450 2E1, points to hydroxylation of 5,8-DHC as additional toxification route, whereas the potentiating effect of 3,5-dinitrocatechol, an inhibitor of catechol-omethyltransferase (COMT, EC 2.1.1.6), points to the o-methylation of hydroxylation products as the detoxification route.

scholarly journals Redox properties and prooxidant cytotoxicity of a neuroleptic agent 6,7-dinitrodihydroquinoxaline-2,3-dione (DNQX).

2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Jonas Šarlauskas ◽  
Aušra Nemeikaitė-Čėnienė ◽  
Lina Misevičienė ◽  
Kastis Krikštopaitis ◽  
Žilvinas Anusevičius ◽  
...  
Keyword(s):  
Electrochemical Reduction ◽  
Bovine Leukemia Virus ◽  
Reduction Potential ◽  
Leukemia Virus ◽  
Redox Properties ◽  
Single Electron ◽  
Reduction Peak ◽  
Neuroleptic Agent ◽  
Electron Reduction ◽  
Dt Diaphorase

In order to characterize the possible mechanism(s) of cytotoxicity of a neuroleptic agent 6,7-dinitrodihydroquinoxaline-2,3-dione (DNQX) we examined the redox properties of DNQX, and its mononitro- (NQX) and denitro- (QX) derivatives. The irreversible electrochemical reduction of the nitro groups of DNQX was characterized by the reduction peak potentials (Ep,7) of -0.43 V and -0.72 V vs. Ag/AgCl at pH 7.0, whereas NQX was reduced at Ep,7 = -0.67 V. The reactivities of DNQX and NQX towards the single-electron transferring enzymes NADPH:cytochrome P-450 reductase and NADPH:adrenodoxin reductase/adrenodoxin complex were similar to those of model nitrobenzenes with the single-electron reduction potential (E¹₇) values of -0.29 V - -0.42 V. DNQX and NQX also acted as substrates for two-electron transferring mammalian NAD(P)H:quinone oxidoreductase (DT-diaphorase). The cytotoxicity of DNQX in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) was prevented by antioxidants and an inhibitor of NQO1, dicoumarol, and was enhanced by the prooxidant alkylating agent 1,3-bis(2-chloromethyl)-1-nitrosourea. A comparison with model nitrobenzene compounds shows that the cytotoxicity of DNQX and NQX reasonably agrees with the ease of their electrochemical reduction, and/or their reactivities towards the used enzymatic single-electron reducing systems. Thus, our data imply that the cytotoxicity of DNQX in FLK cells is exerted mainly through oxidative stress.

Enzymatic Redox Properties of Novel Nitrotriazole Explosives Implications for their Toxicity

2004 ◽  
Vol 59 (5-6) ◽  
pp. 399-404 ◽  
Author(s):  
Jonas Šarlauskas ◽  
Aušra Nemeikaitė-Cėnienė ◽  
Žilvinas Anusevičius ◽  
Lina Misevičienė ◽  
Audronė Marozienė ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leukemia Virus ◽  
The Novel ◽  
Mechanisms Of Toxicity ◽  
Methemoglobin Formation ◽  
Low Toxicity ◽  
Free Radical Formation ◽  
Dt Diaphorase ◽  
Cytochrome P 450 ◽  
Insight Into

The toxicity of conventional nitroaromatic explosives like 2,4,6-trinitrotoluene (TNT) is caused by their enzymatic free radical formation with the subsequent oxidative stress, the formation of alkylating nitroso and/or hydroxylamino metabolites, and oxyhemoglobin oxida­tion into methemoglobin. In order to get an insight into the mechanisms of toxicity of the novel explosives NTO (5-nitro-1,2,4-triazol-3-one) and ANTA (5-nitro-1,2,4-triazol-3-amine), we examined their reactions with the single-electron transferring flavoenzymes NADPH: cytochrome P-450 reductase and ferredoxin:NADP+ reductase, two-electron transferring fla­voenzymes mammalian NAD(P)H:quinone oxidoreductase (DT-diaphorase), and Enterobacter cloacae NAD(P)H:nitroreductase, and their reactions with oxyhemoglobin. The reac­tivity of NTO and ANTA in the above reactions was markedly lower than that of TNT. The toxicity of NTO and ANTA in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) was partly prevented by desferrioxamine and the antioxidant N,N′-diphenyl-p-phenylene diamine, and potentiated by 1,3-bis-(2-chloroethyl)-1-nitrosourea. This points to the involvement of oxidative stress in their cytotoxicity, presumably to the redox cycling of free radicals. The FLK cell line cytotoxicity and the methemoglobin formation in isolated human erythrocytes of NTO and ANTA were also markedly lower than those of TNT, and similar to those of nitrobenzene. Taken together, our data demonstrate that the low toxicity of nitrotriazole explosives may be attributed to their low electron-accepting properties.

scholarly journals Electrochemical, Spectroscopic, and Computational Investigations on Redox Reactions of Selenium Species on Galena Surfaces

Minerals ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 437 ◽  
Author(s):  
Peter Cook ◽  
YoungJae Kim ◽  
Ke Yuan ◽  
Maria C. Marcano ◽  
Udo Becker
Keyword(s):  
Photoelectron Spectroscopy ◽  
Redox Reactions ◽  
Redox Potentials ◽  
Free Energies ◽  
Cathodic Peak ◽  
Redox Transformation ◽  
Hydrogen Electrode ◽  
Midpoint Potential ◽  
Ph Conditions ◽  
Cv Measurements

Despite previous studies investigating selenium (Se) redox reactions in the presence of semiconducting minerals, Se redox reactions mediated by galena (PbS) are poorly understood. In this study, the redox chemistry of Se on galena is investigated over a range of environmentally relevant Eh and pH conditions (+0.3 to −0.6 V vs. standard hydrogen electrode, SHE; pH 4.6) using a combination of electrochemical, spectroscopic, and computational approaches. Cyclic voltammetry (CV) measurements reveal one anodic/cathodic peak pair at a midpoint potential of +30 mV (vs. SHE) that represents reduction and oxidation between HSeO3− and H2Se/HSe−. Two peak pairs with midpoint potentials of −400 and −520 mV represent the redox transformation from Se(0) to HSe− and H2Se species, respectively. The changes in Gibbs free energies of adsorption of Se species on galena surfaces as a function of Se oxidation state were modeled using quantum-mechanical calculations and the resulting electrochemical peak shifts are (−0.17 eV for HSeO3−/H2Se, −0.07 eV for HSeO3−/HSe−, 0.15 eV for Se(0)/HSe−, and −0.15 eV for Se(0)/H2Se). These shifts explain deviation between Nernstian equilibrium redox potentials and observed midpoint potentials. X-ray photoelectron spectroscopy (XPS) analysis reveals the formation of Se(0) potentials below −100 mV and Se(0) and Se(−II) species at potentials below −400 mV.

Redox properties of liver cytochrome P-450

1972 ◽  
Vol 150 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Michael R. Waterman ◽  
H.S. Mason
Keyword(s):  
Redox Properties ◽  
Liver Cytochrome ◽  
Cytochrome P 450

scholarly journals G(AKSL2): a new cell surface antigen of the mouse related to the dualtropic mink cell focus-inducing class of murine leukemia virus detected by naturally occurring antibody.

1979 ◽  
Vol 149 (1) ◽  
pp. 200-215 ◽  
Author(s):  
E Stockert ◽  
A B DeLeo ◽  
P V O'Donnell ◽  
Y Obata ◽  
L J Old
Keyword(s):  
Cell Surface ◽  
Surface Antigen ◽  
Leukemia Virus ◽  
Natural Antibody ◽  
Cell Surface Antigen ◽  
Cytotoxic Action ◽  
Naturally Occurring ◽  
Infected Cells ◽  
Akr Mice

Normal mouse sera were tested for cytotoxic antibody to surface antigens of cultured monolayer cells infected with AKR-derived ecotropic MuLV, xentropic MuLV, or dualtropic MCF 247 MuLV. Antibody to ecotropic MuLV-infected cells was found in a proportion of C57BL/6, C3Hf/Bi, AKR-Fv-1b, and (C3Hf/Bi X AKR)F1 mice, but not AKR or (AKR X C3Hf/Bi)F1 mice. Antibody to xenotropic MuLV-infected cells was virtually restricted to C57BL/6 mice. Antibody to MCF 247-infected cells was found in all strains tested, including AKR mice. Absorption analysis of (C3Hf/Bi x akr)f1 and AKR-Fv-1b sera with selective reactivity for MCF 247-infected cells showed that these sera recognize distinctive antigens on MCF 247-infected cells that are not present on ecotropic or xenotropic MuLV-infected cells. The transplantable AKR spontaneous leukemia AKSL2 was found to be uniquely sensitive to the cytotoxic action of naturally occurring antibody to MCF 247-related antigens and absorption tests with AKSL2 as the target cell and sera from a single AKR-Fv-1b mouse have permitted the definition of a new MuLV-related cell surface antigen, which has been designated G(AKSL2). Thymocytes from young mice of high leukemia-incidence strains (AKR, C58, and PL) express G(AKSL2), whereas thymocytes from 12 other strains do not. In AKR mice, the antigen is expressed in higher amounts on cells from thymus and bone marrow than on spleen cells. All AKR spontaneous leukemias tested express G(AKSL2), as did three MuLV-induced leukemias arising in G(AKSL2)- strains. Five X-ray-induced leukemias of G(AKSL2)- strains were G(AKSL2)-, as were MuLV+ and MuLV- chemically induced sarcomas. In the limited survey conducted to date, natural antibody to G(AKSL2) has been restricted to strains expressing G(AKSL2) in their normal tissues: AKR, AKR congenic mice AKR-Fv-1b and AKR hybrid mice (C3Hf/Bi x akr)f1 and (C57BL/6 X AKR)F1. In vitro G(AKSL2) induction tests involving MuLV infection of cultured monolayer cells showed that 8 of 12 newly isolated dualtropic MuLV shared the property of G(AKSL2) induction with the prototype MCF MuLV, MCF 247. Of the 12 ecotropic MuLV tested, only the N-tropic MuLV isolated from a leukemia originally induced by Passage A Gross virus induced G(AKSL2). The xenotropic and amphotropic MuLV isolates tested lacked G(AKSL2) inducing activity. Recognition of the g(aksl2) system provides a way to trace the origin and natural history of a class of dualtropic MCF MuLV in the mouse and to determine whether natural antibody to G(AKSL2) plays a role in AKR leukemogenesis.

The effect of cytochrome P-450 and reduced glutathione on the ATP-dependent calcium pump of hepatic microsomes from male rats

1986 ◽  
Vol 248 (2) ◽  
pp. 639-645 ◽  
Author(s):  
Jargarlapudi S. Prasad ◽  
Richard R. Erickson ◽  
Daune L. Crankshaw ◽  
Jordan L. Holtzman
Keyword(s):  
Reduced Glutathione ◽  
Calcium Pump ◽  
Male Rats ◽  
Hepatic Microsomes ◽  
Cytochrome P 450

The electrochemical diminution of surface bacterial concentration

1981 ◽  
Vol 27 (10) ◽  
pp. 998-1010 ◽  
Author(s):  
Hari P. Dhar ◽  
Donald H. Lewis ◽  
John O'M. Bockris
Keyword(s):  
Bactericidal Activity ◽  
Phase Contrast ◽  
Dark Field ◽  
Phase Contrast Microscopy ◽  
Bacterial Concentration ◽  
Hydrogen Electrode ◽  
Electrode Potentials ◽  
Contrast Microscopy ◽  
Glass Electrodes ◽  
Normal Hydrogen

An investigation of the electrodic effects on bactericidal activity is presented while applying electrode potentials. Dark-field and phase-contrast microscopy were used to examine regions adjacent to surfaces of SnO2 glass electrodes for bactericidal activity, while scanning electron microscopy (SEM) was used to visualize microbicidal effects on the surfaces of SnO2 electrodes.As the cathode potential approached −0.3 V (normal hydrogen electrode) the bacterial concentration near the cathode was reduced by 99%. The SEM results showed bacterial concentration on cathode to be reduced to 0.1–1% of the original value. Anodes showed reduction of 0.01–1%. The application of the same potential in pulses resulted in enhanced cleaning of the surfaces. The off periods using the pulses could be more than 10 times the on ones.Models considered to explain the observed results involved effects due to change of surface energy with potential, the depletion of O2 in the solution, the production of bactericides (e.g., H2O2), and the change of pH near the surface. Results are inconsistent with the first two models. Many of them are consistent with both the latter two. Diagnostic experiments are suggested.

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