title: Free-radical degradation of high-molecular-weight hyaluronan induced by ascorbate plus cupric ions. Testing of bucillamine and its SA981-metabolite as antioxidants.
abstract: High-molecular-weight hyaluronan (HA) samples were exposed to free-radical chain-degradation reactions induced by ascorbate in the presence of Cu(II) ions - the so-called Weissberger's oxidative system. The concentrations of both reactants [ascorbate, Cu(II)] were comparable to those that may occur during an early stage of the acute phase of joint inflammation. The time-dependent changes of the viscosity of the HA solution in the absence of the substance tested were monitored by rotational viscometry. However, when the anti- or pro-oxidative effects of the antioxidants/drugs were investigated, their dose-dependency was also examined. Additionally, the anti-oxidative activities of these substances were screened by the well-established ABTS and DPPH decolorization assays. The actions of the disease-modifying anti-rheumatic drugs, namely bucillamine and D-penicillamine, were compared to those of L-cysteine and of SA981, the oxidized metabolite of bucillamine. The results indicated that bucillamine was the most efficient scavenger of hydroxyl- and/or peroxyl-type radicals, even at the lowest drug concentration. In contrast, SA981 demonstrated no scavenging activity against the aforementioned free radicals. D-Penicillamine and L-cysteine showed a dual effect, i.e. a pronounced anti-oxidative effect was, after a given time period, followed by a significant pro-oxidative effect.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, SK-84104 Bratislava, Slovakia. valachova4@post.sk
authors.forename: Katarína
authors.initials: K
authors.lastname: Valachová
authors.forename: Eva
authors.initials: E
authors.lastname: Hrabárová
authors.forename: Elena
authors.initials: E
authors.lastname: Priesolová
authors.forename: Milan
authors.initials: M
authors.lastname: Nagy
authors.forename: Mária
authors.initials: M
authors.lastname: Baňasová
authors.forename: Ivo
authors.initials: I
authors.lastname: Juránek
authors.forename: Ladislav
authors.initials: L
authors.lastname: Soltés
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D018501:Antirheumatic Agents / Q000737:chemistry; D001205:Ascorbic Acid / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D017665:Hydroxyl Radical / Q000737:chemistry; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry; D014783:Viscosity
chemical_list: D000975:Antioxidants; D018501:Antirheumatic Agents; D002412:Cations; D005609:Free Radicals; D010545:Peroxides; C513116:bucillamine disulfide; C049375:perhydroxyl radical; D017665:Hydroxyl Radical; D003300:Copper; D006820:Hyaluronic Acid; D010396:Penicillamine; D003545:Cysteine; D001205:Ascorbic Acid; C026535:bucillamine