Metabolism of aqueous soluble nitroxides in hepatocytes: Effects of cell integrity, oxygen, and structure of nitroxides

Iannone, Anna; Hu, Huping; Tomasi, Aldo; Vannini, Vanio; Swartz, Harold M.

doi:10.1016/0304-4165(89)90033-0

Cited by 58 publications

(31 citation statements)

References 28 publications

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“…The initial experiments, however, were not successful due to the rapid bioreduction of the nitroxides employed in the studies with serum. In retrospect, this result was not surprising because those nitroxides were based on the doxy1 or piperidine rings and these are known to be readily bioreduced, especially in very hypoxic tissues ( 12,13,17). The tissue homogenates that we used were quite hypoxic because they were still metabolically active and, therefore, rapidly used up the oxygen which was not resupplied under the conditions of the experiment.…”

Section: An Illustrative Example Of Contrast For Mrsmentioning

confidence: 88%

“…Their usefulness for this purpose has been limited, however, by two factors: their susceptibility to bioreduction and limitations on their effectiveness as relaxers of the protons of water (the latter being the basis of most MRI studies). With increasing study of the interactions of the nitroxides with cells and tissues, it has become possible to develop nitroxides which are more resistant to bioreduction, although this still remains a potentially significant problem if not taken into account (12)(13)(14). Their effectiveness as relaxers for MRI can be increased by an appropriate choice of nitroxide and the method with which it is used (14-16).…”

Section: Introductionmentioning

confidence: 99%

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Contrast agents for magnetic resonance spectroscopy: A method to obtain increased information in in vivo and in vitro spectroscopy

Swartz

Chen

et al. 1991

Magnetic Resonance in Med

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The concept of contrast, which now is an integral part of many magnetic resonance imaging studies, can be extended successfully to magnetic resonance spectroscopy. It involves the use of paramagnetic molecules whose distribution is restricted in some manner, thereby causing differential effects on the NMR spectra. As an illustrative example, the effects of lipophilic nitroxide stable free radicals on the NMR spectra of serum and lipoproteins are shown. These nitroxides differentially broaden away components of the spectra due to the nuclei of methylene and methyl groups, which enables the usually obscured peaks of lactate to be observed fully. The concept can be applied to differential distribution of the contrast agent on the basis of solubility, charge, and/or compartmentalization. It can be used with any type of NMR spectroscopy and any type of paramagnetic contrast (broadening) agent.

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Section: An Illustrative Example Of Contrast For Mrsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Contrast agents for magnetic resonance spectroscopy: A method to obtain increased information in in vivo and in vitro spectroscopy

Swartz

Chen

et al. 1991

Magnetic Resonance in Med

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“…Additionally, inhibition experiments with ascorbate oxidase suggested that ascorbic acid is a main cytosolic reducing agent for pyrrolidine nitroxyl radicals in biological systems (10,27,28). Therefore, mechanisms related to the reduction of nitroxyl radicals should be complicated in biological systems.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging

et al. 2010

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It is widely accepted that redox status, along with the partial pressure of oxygen (pO 2 ), determines the efficacy of some therapeutic methods applied to treat tumors, including radiation. Redox status, evaluated by the reduction of a nitroxyl probe, was reportedly heterogeneous in a mouse tumor model. However, neither variation of heterogeneity of the redox status among mice nor the relation of the redox status to pO 2 in tumors has been characterized sufficiently. In this study, the regional reduction status in a mouse radiation-induced fibrosarcoma tumor model was evaluated using sequential three-dimensional electron paramagnetic resonance (EPR) imaging after i.v. injection of a tissue-permeable nitroxyl probe, HM-PROXYL. The regional decay of HM-PROXYL signal obeyed first-order kinetics, and the amplitude of the reduction rate and extent of its heterogeneity in a tumor varied among six mice. The tissue pO 2 was measured using EPR oximetry with lithium phthalocyanine (LiPc) microcrystals implanted within the tumor. The location of LiPc was determined with EPR imaging. A sequential image was obtained following the injection of HM-PROXYL, even after LiPc implantation, by choosing an HM-PROXYL signal peak which does not overlap with the signal of LiPc. The relationship between pO 2 and the reduction rate at the region of pO 2 measurement was found to be low (r = 0.357) in 13 tumor-bearing mice, indicating that the extent of oxygenation does not necessarily affect the redox status under air-breathing conditions. The results strongly indicate the necessity of measurements of both redox status and oxygenation in every tumor to characterize tumor physiology. Cancer Res; 70(10); 4133-40. ©2010 AACR.

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“…Hepatocytes were isolated using a modification of the method described by Iannone et al (1989). For anesthesia and to prevent blood coagulation, fed rats were given i.p., a 200 ll/100 g b.w.…”

Section: Hepatocytes Isolationmentioning

confidence: 99%

Conjugated linoleic acid isomers modulate protein expression profile in rat hepatocytes

et al. 2012

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Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid, which has been recently proven to be effective in reducing body fat mass, but brings as a side effect, the liver enlargement due to an increased lipid content. The in vivo lipogenic activity has been suggested to be due to the reduction in fat mass and to the consequent metabolism of blood glucose to fatty acid in the liver rather than in the adipose tissue. We investigated the ability of CLA to directly induce steatosis by modulating the expression pattern of hepatic proteins involved in lipid metabolism. To avoid interferences derived from CLA metabolism by other tissues, we used the in vitro model of freshly isolated rat hepatocytes incubated in the presence of different CLA isomers. The direct effect of CLA on lipid accumulation in hepatocytes was demonstrated by the altered expression pattern of several proteins involved in lipid metabolism, as assessed by two-dimensional gel electrophoresis and confirmed by Western blotting analysis. The CLA isomer c9,t11 was most effective in modulating the protein expression profile.

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Metabolism of aqueous soluble nitroxides in hepatocytes: Effects of cell integrity, oxygen, and structure of nitroxides

Cited by 58 publications

References 28 publications

Contrast agents for magnetic resonance spectroscopy: A method to obtain increased information in in vivo and in vitro spectroscopy

Contrast agents for magnetic resonance spectroscopy: A method to obtain increased information in in vivo and in vitro spectroscopy

Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging

Conjugated linoleic acid isomers modulate protein expression profile in rat hepatocytes

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