Study of pro- and anti-oxidative properties of D-penicillamine in a system comprising high-molar-mass hyaluronan, ascorbate, and cupric ions.

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.

[1]  K. Valachová,et al.  HYALURONAN DEGRADATION BY ASCORBATE: PROTECTIVE EFFECTS OF MANGANESE(II) CHLORIDE , 2008 .

[2]  L. Šoltés,et al.  Degradation of high-molar-mass hyaluronan by an oxidative system comprising ascorbate, Cu(II), and hydrogen peroxide: inhibitory action of antiinflammatory drugs--naproxen and acetylsalicylic acid. , 2007, Journal of pharmaceutical and biomedical analysis.

[3]  K. Valachová,et al.  Solution properties of high-molar-mass hyaluronans: the biopolymer degradation by ascorbate. , 2007, Carbohydrate research.

[4]  L. Šoltés,et al.  Unexplored capabilities of chemiluminescence and thermoanalytical methods in characterization of intact and degraded hyaluronans , 2006 .

[5]  M. Eisenmann-Klein,et al.  Increased levels of transition metals in breast cancer tissue. , 2006, Neuro endocrinology letters.

[6]  L. Šoltés,et al.  Degradative action of reactive oxygen species on hyaluronan. , 2006, Biomacromolecules.

[7]  K. Valachová,et al.  The degradative action of peroxynitrite on high-molecular-weight hyaluronan. , 2006, Neuro endocrinology letters.

[8]  L. Šoltés,et al.  Study of Hyaluronan Degradation by Means of Rotational Viscometry: Contribution of the Material of Viscometer , 2004 .

[9]  C. Chow,et al.  Copper toxicity, oxidative stress, and antioxidant nutrients. , 2003, Toxicology.

[10]  K M Williams,et al.  Enantiomers in arthritic disorders. , 1990, Pharmacology & therapeutics.

[11]  R. Messner,et al.  In vitro production and scavenging of hydrogen peroxide by D-penicillamine. Relationship to copper availability. , 1985, Arthritis and rheumatism.

[12]  W. Niedermeier,et al.  Trace metal composition of synovial fluid and blood serum of patients with rheumatoid arthritis. , 1971, Journal of chronic diseases.