Valachova Katarina, Hrabarova Eva, Gemeiner Peter, Soltes Ladislav
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia.
Neuro Endocrinol Lett. 2008 Oct;29(5):697-701.
The study presents results of pro- and anti-oxidative effects of D-penicillamine on hyaluronan degradation by ascorbate plus cupric ions.
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.
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.
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.
本研究展示了D-青霉胺对抗坏血酸加铜离子所致透明质酸降解的促氧化和抗氧化作用结果。
使用了由高分子量透明质酸以及抗坏血酸加铜离子组成的成熟降解体系。首先，研究了在该体系中用D-青霉胺替代抗坏血酸的效果。然后，在反应开始前或反应开始1小时后将D-青霉胺添加到上述降解体系中。为监测透明质酸降解动力学，采用了旋转粘度测定法。
当用D-青霉胺替代抗坏血酸时，未发生透明质酸降解。在反应开始时将该药物添加到完整的降解体系中会导致透明质酸降解受到显著抑制。然而，约1小时内抑制作用转变为促氧化作用。
D-青霉胺对透明质酸降解的双重作用可能与以下因素有关：（i）该药物在有氧条件下完全捕获抗坏血酸加铜离子产生的OH自由基；（ii）D-青霉胺产生的硫自由基与D-青霉胺阴离子反应生成新的自由基反应物种，例如通过还原双氧分子可产生更多OH自由基。
