Direct Electrochemical Measurement of Nitric Oxide Production by Cytochrome P450-catalyzed Oxidation of N,N′-Substituted Hydroxyguanidines

Trevin, Stéphane; Andre, Sandrine; Devynck, Jacques; Boucher, Jean Luc; Bedioui, Féthi

doi:10.1039/a608091j

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…These experiments clearly showed that NO itself is formed during those oxidations; however, they did not allow us to quantify its formation. Measurement of steady-state concentrations of NO during oxidation of NOHA, 1a, 12, and 13 by DEX-treated rat liver microsomes in electrochemical experiments using a specific electrode (42) also led to the conclusion that free NO is formed during those oxidations (43).…”

Section: Results (1) Oxidation Of N-(4-chlorophenyl)-n′-hydroxy Guani...mentioning

confidence: 99%

Microsomal Cytochrome P450 Dependent Oxidation of N-Hydroxyguanidines, Amidoximes, and Ketoximes: Mechanism of the Oxidative Cleavage of Their CN(OH) Bond with Formation of Nitrogen Oxides

et al. 1998

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Oxidation by rat liver microsomes of 13 compounds involving a C=N(OH) function (including N-hydroxyguanidines, amidoximes, ketoximes, and aldoximes) was found to occur with the release of nitrogen oxides such as NO, NO2-, and NO3-. The greatest activities were observed with liver microsomes from dexamethasone-treated rats (up to 8 nmol of NO2- nmol of P450(-)1 min-1). A detailed study of the microsomal oxidation of some of these compounds was performed. Oxidation of N-(4-chlorophenyl)-N'-hydroxy-guanidine led to the formation of the corresponding urea and cyanamide in addition to NO, NO2-, and NO3-. Formation of all these products was dependent on NADPH, O2, and cytochromes P450. Oxidation of two arylamidoximes was found to occur with formation of the corresponding amides and nitriles in addition to nitrogen oxides. Oxidation of 4-(chlorophenyl)methyl ketone oxime gave the corresponding ketone and nitroalkane as well as NO, NO2-, and NO3-. These reactions were also dependent on cytochromes P450 and required NADPH and O2. Mechanistic experiments showed that microsomal oxidations of amidoximes to the corresponding nitriles and of ketoximes to the corresponding nitroalkanes are not inhibited by superoxide dismutase (SOD) and are performed by a cytochrome P450 active species, presumably the high-valent P450-iron-oxo complex. On the contrary, microsomal oxidation of N-hydroxyguanidines to the corresponding cyanamides was greatly inhibited by SOD and appeared to be mainly due to O2*- derived from the oxidase function of cytochromes P450. Similarly, microsomal oxidations of N-hydroxyguanidines and amidoximes to the corresponding ureas and amides were also found to be mainly performed by O2*-, as shown by the great inhibitory effect of SOD (70-100%) and the ability of the xanthine-xanthine oxidase system to give similar oxidation products. However, it is noteworthy that other species, such as the P450 Fe(II)-O2 complex, are also involved, to a minor extent, in the SOD-insensitive microsomal oxidative cleavages of compounds containing a C=N(OH) bond. Our results suggest a general mechanism for such oxidative cleavages of C=N(OH) bonds with formation of nitrogen oxides by cytochromes P450 and NO-synthases, with the involvement of O2*- and its Fe(III) complex [(FeIII-O2-) or (FeII-O2)] as main active species.

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Section: Results (1) Oxidation Of N-(4-chlorophenyl)-n′-hydroxy Guani...mentioning

confidence: 99%

Microsomal Cytochrome P450 Dependent Oxidation of N-Hydroxyguanidines, Amidoximes, and Ketoximes: Mechanism of the Oxidative Cleavage of Their CN(OH) Bond with Formation of Nitrogen Oxides

et al. 1998

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“…17 Nafioncoated carbon fiber electrodes also have been applied to cellular NO measurement. [18][19][20][21][22][23][24] A fiber-optic chemical sensor was also applied to selective NO measurement; [25][26][27][28] hemoprotein labeled with a fluorescent dye was incorporated in the sensor tip, and changes in the dye's intensity or fluorescence lifetime by NO binding due to cell response was measured.…”

mentioning

confidence: 99%

“…Clark type electrodes were used to measure NO from brain tissues or NO in various biological systems. − A Pt/Ir alloy working electrode whose tip was covered with three different membranes was used for selective NO measurement . Nafion-coated carbon fiber electrodes also have been applied to cellular NO measurement. − A fiber-optic chemical sensor was also applied to selective NO measurement; − hemoprotein labeled with a fluorescent dye was incorporated in the sensor tip, and changes in the dye's intensity or fluorescence lifetime by NO binding due to cell response was measured.…”

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confidence: 99%

Microcoaxial Electrode for in Vivo Nitric Oxide Measurement

et al. 2000

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Nitric oxide (NO) is a gaseous mediator involved in various physiological phenomena, such as vasorelaxation and neurotransmission. Investigation of local cellular responses of NO production in vivo and in vitro requires a measurement method with a high spatial resolution. For selective NO measurement, we therefore developed a microcoaxial electrode whose tip diameter is less than 10 microm. Calibration using various concentrations of NO (0.1-1.0 microM) showed that the electrode has good linearity (r = 0.99) and its detection limit is 0.075 microM (S/N = 3). We verified the applicability of this electrode to in vivo and in vitro local measurement NO released from bovine aortic cultured endothelial cells (BAECs) stimulated by acetylcholine (ACh). After the addition of ACh, a transient increase in NO concentration was detected by the electrode. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), a putative NO synthase inhibitor, NO release (peak NO concentration) from RAECs was significantly less than that in the absence of L-NAME (0.18 +/- 0.04 microM vs 0.47 +/- 0.13; P < 0.01). After removal of L-NAME, NO release partially recovered (0.39 +/- 0.10 microM). In conclusion, the microcoaxial electrode was successfully applied to direct and continuous NO measurement in biological systems.

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“…2). N-hydroxyguanidine is a known electrochemically active species, 26,27 and a clear oxidation and reduction peak was observed from the N-hydroxyguanidine at +355 mV and +250 mV vs Ag/AgCl respectively (Fig. 3a).…”

Section: Resultsmentioning

confidence: 99%

Elucidating the Electrochemical Mechanism of N^G-Hydroxy-L-Arginine

Arral

Tooley

Ziino

et al. 2020

J. Electrochem. Soc.

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NG-Hydroxy-L-arginine (NOHA) is a stable intermediate product in the urea cycle that can be used to monitor the consumption of L-arginine by nitrous oxide synthase (NOS) to produce nitric oxide (NO) and L-citrulline. Research has implicated the urea cycle in many diseases and NO has cultivated interest as a potential biomarker for neural health. Electrochemical detection is an established, cost-effective method that can successfully detect low levels of analyte concentrations. As one of the few electrochemically active species in the urea cycle, NOHA shows promise as a biomarker for monitoring disruptions in this biochemical process. In this study, we show that NOHA has an oxidation peak at +355 mV vs Ag/AgCl at a glassy carbon electrode. In addition, cyclic voltammetry studies with structural analogs—alanine and N-hydroxyguanidine—allowed us to approximate the oxidation wave at +355 mV vs Ag/AgCl to be a one electron process. Diffusivity of NOHA was found using linear scan voltammetry with a rotating disk electrode and approximated at 5.50 × 10−5 cm2 s−1. Ample work is still needed to make a robust biosensor, but the results here characterize the electrochemical activity and represent principle steps in making a NOHA biosensor.

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Direct Electrochemical Measurement of Nitric Oxide Production by Cytochrome P450-catalyzed Oxidation of N,N′-Substituted Hydroxyguanidines

Cited by 5 publications

References 23 publications

Microsomal Cytochrome P450 Dependent Oxidation of N-Hydroxyguanidines, Amidoximes, and Ketoximes: Mechanism of the Oxidative Cleavage of Their CN(OH) Bond with Formation of Nitrogen Oxides

Microsomal Cytochrome P450 Dependent Oxidation of N-Hydroxyguanidines, Amidoximes, and Ketoximes: Mechanism of the Oxidative Cleavage of Their CN(OH) Bond with Formation of Nitrogen Oxides

Microcoaxial Electrode for in Vivo Nitric Oxide Measurement

Elucidating the Electrochemical Mechanism of N^G-Hydroxy-L-Arginine

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Direct Electrochemical Measurement of Nitric Oxide Production by Cytochrome P450-catalyzed Oxidation of N,N′-Substituted Hydroxyguanidines

Cited by 5 publications

References 23 publications

Microsomal Cytochrome P450 Dependent Oxidation of N-Hydroxyguanidines, Amidoximes, and Ketoximes: Mechanism of the Oxidative Cleavage of Their CN(OH) Bond with Formation of Nitrogen Oxides

Microsomal Cytochrome P450 Dependent Oxidation of N-Hydroxyguanidines, Amidoximes, and Ketoximes: Mechanism of the Oxidative Cleavage of Their CN(OH) Bond with Formation of Nitrogen Oxides

Microcoaxial Electrode for in Vivo Nitric Oxide Measurement

Elucidating the Electrochemical Mechanism of NG-Hydroxy-L-Arginine

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Elucidating the Electrochemical Mechanism of N^G-Hydroxy-L-Arginine