title: Ascorbate and Cu(II)-induced oxidative degradation of high-molar-mass hyaluronan. Pro- and antioxidative effects of some thiols.
abstract: OBJECTIVE
  This study presents the results of antioxidative and pro-oxidative efficacy of cysteamine and D-penicillamine (D-pen) in comparison to L-glutathione (L-GSH) on high-molar-mass hyaluronan (HA) degradation by cupric ions plus ascorbic acid.
  
  
  METHODS
  The substance tested was applied in the degradative system cupric ions plus ascorbate: (i) before the reaction onset or also (ii) 1 h after the reaction started. The results obtained were compared with that one recorded by using the degradative system in the absence of the substance tested. To monitor HA degradation kinetics, rotational viscometry was applied. Moreover, the standard ABTS and DPPH assays were used.
  
  
  RESULTS
  By using the method of rotational viscometry, D-pen showed dual effect: initial inhibitory effect on •OH radicals was changed to a pro-oxidative one in the dose and time dependent manner. Both L-GSH and cysteamine were recorded to be more effective scavengers of •OH radicals than D-pen. Cysteamine demonstrated to be an excellent scavenger also of alkoxyl- and peroxyl- type radicals. Based on IC50 values, gained by ABTS assay, it is evident that D-pen showed higher radical scavenging capacity compared to cysteamine. Similar results were observed also in DPPH assay, although in this assay less effective radical scavenging capacities of both substances tested were recorded.
  
  
  CONCLUSIONS
  On the basis of the results obtained, it can be stated that D-pen can produce hydrogen peroxide or •OH radicals and can inhibit the production of these oxidants. Our results showed that both L-GSH and cysteamine are similarly effective in inhibiting of HA degradation. Moreover, cysteamine demonstrated to be a significant inhibitor of alkoxyl- and peroxyl- type radicals generated from C-type macroradical of HA.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. katarina.valachova@savba.sk
authors.forename: Katarina
authors.initials: K
authors.lastname: Valachova
authors.forename: Eva
authors.initials: E
authors.lastname: Hrabarova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Drafi
authors.forename: Ivo
authors.initials: I
authors.lastname: Juranek
authors.forename: Katarina
authors.initials: K
authors.lastname: Bauerova
authors.forename: Elena
authors.initials: E
authors.lastname: Priesolova
authors.forename: Milan
authors.initials: M
authors.lastname: Nagy
authors.forename: Ladislav
authors.initials: L
authors.lastname: Soltes
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D003543:Cysteamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010396:Penicillamine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D006878:Hydroxides; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D003543:Cysteamine; D003300:Copper; D006820:Hyaluronic Acid; C031356:hydroxide ion; D006861:Hydrogen Peroxide; D005978:Glutathione; D010396:Penicillamine; D001205:Ascorbic Acid