Electron paramagnetic resonance spectrometry evidence for bioreduction of tirapazamine to oxidising free radicals under anaerobic conditions

Patterson, Laurence H.; Taiwo, Fatai A.

doi:10.1016/s0006-2952(00)00487-1

Cited by 30 publications

(39 citation statements)

References 4 publications

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“…We have shown that the HUVECs produce a nearly linear increase in the amount of free radical generated in the solution, this free radical being most likely hydroxyl, because the EPR parameters of the predominant radical obtained are characteristic of the hydroxyl radical. We have shown in previous studies that the simultaneous presence of superoxide and hydroxyl radicals in a composite spectrum with carboncentered radicals is resolvable (43). Therefore, any significant presence of the superoxide radical anion in the copper-Hcy reaction would have been observed by EPR spectrometry; thus, we are confident that the major radical present is hydroxyl.…”

Section: Hcy Exported From Endothelial Cells Oxidizes Ldl Via the Hydmentioning

confidence: 62%

Downstream effects on human low density lipoprotein of homocysteine exported from endothelial cells in an in vitro system

Nakano

Taiwo

Nugent

et al. 2005

Journal of Lipid Research

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A model system is presented using human umbilical vein endothelial cells (HUVECs) to investigate the role of homocysteine (Hcy) in atherosclerosis. HUVECs are shown to export Hcy at a rate determined by the flux through the methionine/Hcy pathway. Additional methionine increases intracellular methionine, decreases intracellular folate, and increases Hcy export, whereas additional folate inhibits export. An inverse relationship exists between intracellular folate and Hcy export. Hcy export may be regulated by intracellular S -adenosyl methionine rather than by Hcy. Human LDLs exposed to HUVECs exporting Hcy undergo time-related lipid oxidation, a process inhibited by the thiol trap dithionitrobenzoate. This is likely to be related to the generation of hydroxyl radicals, which we show are associated with Hcy export. Although Hcy is the major oxidant, cysteine also contributes, as shown by the effect of glutamate. Finally, the LDL oxidized in this system showed a time-dependent increase in uptake by human macrophages, implying an upregulation of the scavenger receptor. These results suggest that continuous export of Hcy from endothelial cells contributes to the generation of extracellular hydroxyl radicals, with associated oxidative modification of LDL and incorporation into macrophages, a key step in atherosclerosis. Factors that regulate intracellular Hcy metabolism modulate these effects. -Nakano, E.,

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Section: Hcy Exported From Endothelial Cells Oxidizes Ldl Via the Hydmentioning

confidence: 62%

Downstream effects on human low density lipoprotein of homocysteine exported from endothelial cells in an in vitro system

Nakano

Taiwo

Nugent

et al. 2005

Journal of Lipid Research

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“…In an early publication, tiron had been reported to protect cells against aerobic toxicity of tirapazamine (SR4233), a proposed anticancer drug [6]. In a more recent publication we demonstrated the formation of radicals from the bioreduction of tirapazamine [9]. These radicals, we concluded, were the cytotoxic species derived from the pro-drug and essential for disrupting cellular processes in-hypoxia.…”

Section: Introductionmentioning

confidence: 74%

“…Detection of the superoxide radical anion, formed in the xanthine oxidase-catalysed oxidation of xanthine, by EPR spectroscopy was facilitated by spin trapping using DMPO. The DMPO-OOH adduct has a characteristic 12-line spectrum; a N = 1.43 mT, a H 1 = 1.15 mT, a H 2 = 0.13 mT [9], shown in Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

Mechanism of tiron as scavenger of superoxide ions and free electrons

Taiwo

2008

Spectroscopy

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Sodium 4,5-dihydroxybenzene-1,3-disulfonate (tiron) has been reported to be an efficient chelator of certain metal ions, and a substrate in several enzyme reactions. Its small size facilitates cell entry and therefore modulates intracellular electron transfer reactions as an antioxidant by scavenging free radicals. Its reduction by electrochemical and enzymatic methods gives identical products; a semiquinone detectable by EPR spectroscopy. In a test of its use as a spin trap, in comparison with DMPO, tiron does not form a molecular spin-adduct but proves more functional as an electron trap. Electron addition to tiron is more facile than reduction of dioxygen as observed by the non-formation of DMPO-OOH spin-adduct in the system XO/HPX/O2/DMPO/tiron. Rather, it is the tiron semiquinone radical which is formed quantitatively with increasing concentration of hypoxanthine independent of oxygen concentration. These results offer explanation for the action of tiron and its suitability for measuring electron release in hypoxic conditions, and also for mitigating redox-induced toxicity in drug regimes by acting as an electron scavenger.

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“…To clarify the mechanism by which the ozone microbubble solution acts on the photoresist, we performed ESR measurements by the spin-trap method. 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was used as the spin-trap reagent because it has been widely used to identify oxygen-centered radicals such as superoxide and the hydroxyl radical [12][13][14][15][16].…”

Section: Determination Of Hydroxyl Radical Generation By Esr Measurementmentioning

confidence: 99%

Effect of Microbubbles on Ozonized Water for Photoresist Removal

Takahashi

Horibe

Matsuura

et al. 2015

J. Photopol. Sci. Technol.

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The existence of microbubbles in ozonized water has been shown to significantly enhance the photoresist removal rate due to an elevated dissolved ozone concentration and a direct effect of the microbubbles relating to the radical generation. Additionally, the ozone microbubble solution was able to effectively remove a high-dose ion-implanted photoresist, which is extremely resistant to removal by ozonized water and other wet chemicals because of its amorphous carbon-like layer, or "crust". Electron spin resonance experiments were also performed without the influence of serious metal contamination and indicated the presence of hydroxyl radicals, which are thought to be formed by interaction of ozone with hydroxide ions adsorbed at the gas-water interface upon collapse of the microbubbles.

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Electron paramagnetic resonance spectrometry evidence for bioreduction of tirapazamine to oxidising free radicals under anaerobic conditions

Cited by 30 publications

References 4 publications

Downstream effects on human low density lipoprotein of homocysteine exported from endothelial cells in an in vitro system

Downstream effects on human low density lipoprotein of homocysteine exported from endothelial cells in an in vitro system

Mechanism of tiron as scavenger of superoxide ions and free electrons

Effect of Microbubbles on Ozonized Water for Photoresist Removal

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