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Journal Article 2012; 33(Suppl 3): 151-154 PubMed PMID: 23353859 Citation  Keywords:  Antioxidants:chemistry, Ascorbic Acid:chemistry, Copper:chemistry, Cysteine:analogs & derivatives, Extracellular Matrix:chemistry, Free Radicals:chemistry, Humans, Hyaluronic Acid:chemistry, Molecular Weight, Oxidation-Reduction, Spectroscopy, Fourier Tra.   

OBJECTIVES: Hyaluronan (HA), one of the main components of extracellular matrix, is a glycosaminoglycan composed of repeating disaccharide units of N-acetyl-d-glucosamine and d-glucuronic acid linked by β-(1→4) and β-(1→3) glycoside bonds. High-molar-mass HA was used as a model for studying its oxidative degradation. In the present paper protective effects of bucillamine against the free-radical degradation of HA were investigated. The HA fragments generated were characterized as well.

METHODS: To induce free-radical-mediated degradation of high-molar-mass HA under aerobic conditions, we applied Weissberger's oxidative system, comprising biogenic compounds in relevant pathophysiological concentrations, i.e. 100 µM ascorbate plus 1 µM Cu(II). Time-dependent decreases of dynamic viscosity of the HA solutions were recorded by rotational viscometry. Electron donor behaviors of bucillamine were studied by a standard ABTS test method and a chemiluminescence (CL) assay. Ability of incorporation of generated bucillamine thiyl radicals into the biopolymer was verified by Fourier-transform infrared spectroscopy (FT-IR) and size exclusion chromatography with a multi-angle light scattering photometer (SEC-MALS).

RESULTS: Decrease of HA viscosity reflected HA degradation. The drug tested was applied in two arrangements: to prevent •OH radical generation (1) and ROO• type radicals propagation (2). Bucillamine, which acted as an efficient •H donor, is also a proper electron donor, as proved by ABTS and CL assays. FT-IR and SEC-MALS methods showed that the drug tested did not incorporate into the biopolymer chains.

CONCLUSION: Bucillamine significantly protected high-molar-mass HA against free-radical degradation in vitro, and supposedly this positive action of the drug may be involved in its beneficial effect observed in clinical practice....

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Journal Article 2008; 29(5): 697-701 PubMed PMID: 18987579 Citation  Keywords:  Antioxidants:chemistry, Ascorbic Acid:chemistry, Carbohydrate Sequence, Copper:chemistry, Free Radicals:chemistry, Hyaluronic Acid:chemistry, Hydrogen Peroxide:chemistry, Hydroxyl Radical:chemistry, Kinetics, Molecular Weight, Oxidants:chemistry, Penicill.   

OBJECTIVES: The study presents results of pro- and anti-oxidative effects of D-penicillamine on hyaluronan degradation by ascorbate plus cupric ions.

METHODS: The well established degradative system comprising high-molar-mass hyaluronan and ascorbate plus Cu(II) ions was used. Primarily, the effects of replacement of ascorbic acid in this system by D-penicillamine were investigated. Then, D-penicillamine was added into the above degradative system before reaction onset or 1h after the reaction had started. To monitor hyaluronan degradation kinetics, rotational viscometry was applied.

RESULTS: No hyaluronan degradation occurred when ascorbate was replaced by D-penicillamine. The drug addition into the complete degradative system at the reaction onset caused a marked inhibition of hyaluronan degradation. However, the inhibitory effect turned to a pro-oxidative one within appr. 1 h.

CONCLUSION: The dual behavior of D-penicillamine on hyaluronan degradation can relate to: (i) the drug completely traps *OH radicals generated from ascorbate plus Cu(II) ions under aerobic conditions; (ii) thiyl radicals generated from D-penicillamine react with D-penicillamine anions resulting in novel radical reactive species, which e.g. by reducing dioxygen molecules can generate further *OH radicals....

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Journal Article 2005; 26(3): 247-252 PubMed PMID: 15990730 Citation  Keywords:  Animals, Copper:chemistry, Gonadotropin-Releasing Hormone:chemistry, Metals, Heavy:chemistry, Nickel:chemistry, Nuclear Magnetic Resonance, Biomolecular, Protons, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization,.   

: MALDI-TOF mass spectrometry, 1H NMR spectrometry, the continuous variation method and molecular modeling by MM3 calculation confirmed our earlier studies showing that gonadotropin-releasing hormone (GnRH) forms complex with copper(II) ion with the binding ratio 1:1. The copper(II) complex formed at physiological pH has a square planar configuration and GnRH complexes with nickel(II) and cobalt(II) ions are less stable than that of copper(II)....

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