Antimutagenic and Anticarcinogenic Mechanisms of Aminothiols

Inflammatory joint diseases are of considerable socio-economic significance. However, mechanisms of cartilage destruction are so far only poorly understood. This review is dedicated to reactive oxygen species (ROS) like superoxide anion radicals, hydrogen peroxide, singlet oxygen, hypochlorous acid, hydroxyl radicals and nitric oxide that are generated under inflammatory conditions and also to their potential contribution to cartilage degradation. First, the relevance of rheumatic diseases and potential mechanisms of cartilage degradation are discussed in this review, followed by the description of the chemical constituents and the molecular architecture of articular cartilage as well as the different cell types that play a role in inflammation and cartilage destruction. Methods of the assessment of cartilage degeneration are also shortly discussed. In the main chapter of this review the characteristics of individual ROS, their generation under in vivo conditions as well as their reactivities with individual cartilage components are discussed. Because of the low selectivity of ROS, useful "markers" of cartilage degradation allowing the differentiation of effects induced by individual ROS are also discussed. In the last chapter current therapeutic concepts of the treatment of rheumatic diseases are reviewed. The recently developed "anti-TNF-alpha" therapy that is primarily directed against neutrophilic granulocytes that are powerful sources of ROS and, therefore, important mediators of joint degeneration are emphasised.

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“…8). The unusual high reactivity of cysteine with ROS is the reason why it is often used as an antioxidant [84].…”

Section: Further Important Reactions Of Omentioning

confidence: 99%

Contribution of Reactive Oxygen Species to Cartilage Degradation in Rheumatic Diseases: Molecular Pathways, Diagnosis and Potential Therapeutic Strategies

Schiller¹,

Fuchs²,

Arnhold³

et al. 2003

Current Medicinal Chemistry

116

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“…[1][2][3] Research has shown that N-AC has potential both as a chemo-preventative agent and as a treatment in certain types of cancer, including lung, skin, head, neck, mammary, and liver cancers. 4,5 The determination of N-AC has been established by such methods as chromatography, [6][7][8] spectrophotometry, [9][10][11][12] fluorimetry, 13 flow injection, 14 and electrochemical methods. 15,16 Folic acid (FA) is a water-soluble vitamin.…”

Section: Introductionmentioning

confidence: 99%

Modified multiwalled carbon nanotubes paste electrode as a sensor for the electrocatalytic determination of N-acetylcysteine in the presence of high concentrations of folic acid

et al. 2012

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“…Chromium(VI) is an established carcinogen , and a potent mutagen for bacterial and mammalian cells. , The generally accepted mechanism for the biological action of Cr(VI) − includes the following: (i) uptake by cells through anion channels (for [CrO 4 ] 2- ) or through phagocytosis (for insoluble chromates); (ii) intracellular reduction of Cr(VI) to Cr(III) with the formation of reactive Cr(V), Cr(IV), and free radical intermediates, capable of damaging DNA; (iii) stabilization of Cr(V) and Cr(IV) species by intracellular ligands such as 1,2-diolates and 2-hydroxycarboxylates; and (iv) formation of kinetically inert Cr(III) complexes with biological macromolecules as the products of Cr(VI) reductions. Glutathione (GSH) and ascorbate are the most likely intracellular reductants of Cr(VI); , therefore, their ability to stabilize the Cr(V) oxidation state 11-16 is important in relation to Cr(VI)-induced genotoxicity and carcinogenicity. , Formation of Cr(V) complexes during the reactions of Cr(VI) with GSH has been studied by EPR spectroscopy; − however, the nature of these Cr(V) species remained unclear .…”

Section: Introductionmentioning

confidence: 99%

Structure and Reactivity of a Chromium(V) Glutathione Complex¹

2003

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Chromium(V) glutathione complexes are among the likely reactive intermediates in Cr(VI)-induced genotoxicity and carcinogenicity. The first definitive structure of one such complex, [Cr(V)O(LH(2))(2)](3)(-) (I; LH(5) = glutathione = GSH), isolated from the reaction of Cr(VI) with excess GSH at pH 7.0 (O'Brien, P.; Pratt, J.; Swanson, F. J.; Thornton, P.; Wang, G. Inorg. Chim. Acta 1990, 169, 265-269), has been determined by a combination of electrospray mass spectrometry (ESMS), X-ray absorption spectroscopy (XAS), EPR spectroscopy, and analytical techniques. In addition, Cr(V) complexes of GSH ethyl ester (gamma-Glu-Cys-GlyOEt) have been isolated and characterized by ESMS, and Cr(III) products of the Cr(VI) + GSH reaction have been isolated and characterized by ESMS and XAS. The thiolato and amido groups of the Cys residue in GSH are responsible for the Cr(V) binding in I. The Cr-ligand bond lengths, determined from multiple-scattering XAFS analysis, are as follows: 1.61 A for the oxo donor; 1.99 A for the amido donors; and 2.31 A for the thiolato donors. A significant electron withdrawal from the thiolato groups to Cr(V) in I was evident from the XANES spectra. Rapid decomposition of I in aqueous solutions (pH = 1-13) occurs predominantly by ligand oxidation with the formation of Cr(III) complexes of GSH and GSSG. Maximal half-lives of the Cr(V) species (40-50 s at [Cr] = 1.0 mM and 25 degrees C) are observed at pH 7.5-8.0. The experimental data are in conflict with a recent communication (Gaggelli, E.; Berti, F.; Gaggelli, N.; Maccotta, A.; Valensin, G. J. Am. Chem. Soc. 2001, 123, 8858-8859) on the formation of a Cr(V) dimer as a major product of the Cr(VI) + GSH reaction, which may have resulted from misinterpretation of the ESMS and NMR spectroscopic data.

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Antimutagenic and Anticarcinogenic Mechanisms of Aminothiols

Cited by 17 publications

References 26 publications

Contribution of Reactive Oxygen Species to Cartilage Degradation in Rheumatic Diseases: Molecular Pathways, Diagnosis and Potential Therapeutic Strategies

Contribution of Reactive Oxygen Species to Cartilage Degradation in Rheumatic Diseases: Molecular Pathways, Diagnosis and Potential Therapeutic Strategies

Modified multiwalled carbon nanotubes paste electrode as a sensor for the electrocatalytic determination of N-acetylcysteine in the presence of high concentrations of folic acid

Structure and Reactivity of a Chromium(V) Glutathione Complex¹

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Antimutagenic and Anticarcinogenic Mechanisms of Aminothiols

Cited by 17 publications

References 26 publications

Contribution of Reactive Oxygen Species to Cartilage Degradation in Rheumatic Diseases: Molecular Pathways, Diagnosis and Potential Therapeutic Strategies

Contribution of Reactive Oxygen Species to Cartilage Degradation in Rheumatic Diseases: Molecular Pathways, Diagnosis and Potential Therapeutic Strategies

Modified multiwalled carbon nanotubes paste electrode as a sensor for the electrocatalytic determination of N-acetylcysteine in the presence of high concentrations of folic acid

Structure and Reactivity of a Chromium(V) Glutathione Complex1

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Structure and Reactivity of a Chromium(V) Glutathione Complex¹