Betts W H, Cleland L G
Arthritis Rheum. 1982 Dec;25(12):1469-76. doi: 10.1002/art.1780251213.
Degradation of hyaluronic acid (measured viscometrically) by oxygen-derived free radicals (ODFR) generated 1) by autoxidation of ferrous EDTA chelates and 2) enzymatically by xanthine oxidase and hypoxanthine (XO/HX) was studied. Degradation of hyaluronic acid by XO/HX was strongly inhibited by superoxide dismutase and catalase, whereas degradation of hyaluronic acid by autoxidation of ferrous ions was weakly inhibited by catalase and unaffected by superoxide dismutase. Both ODFR-producing systems were inhibited by hydroxyl radical scavengers, suggesting that hydroxyl radical was the proximate damaging species in both systems. Penicillamine at concentrations of 1-5 mM stimulated hyaluronic acid degradation by ferrous EDTA chelates but inhibited degradation by the XO/HX system. Higher concentrations of penicillamine and all concentrations studied (1-100 mM) of other antiinflammatory drugs (chloroquine, gold sodium thiomalate, and salicylate) inhibited hyaluronic acid degradation by both the autoxidation and enzymatic ODFR-producing systems, with inhibitory potency similar to that seen with known hydroxyl radical scavengers. Both systems serve as in vitro models of ODFR-mediated tissue damage which may occur in vivo at sites of inflammation.
研究了由1）亚铁乙二胺四乙酸螯合物的自氧化和2）黄嘌呤氧化酶和次黄嘌呤（XO/HX）酶促产生的氧衍生自由基（ODFR）对透明质酸的降解作用（通过粘度测定法测量）。超氧化物歧化酶和过氧化氢酶强烈抑制XO/HX对透明质酸的降解，而亚铁离子自氧化对透明质酸的降解仅受到过氧化氢酶的微弱抑制，且不受超氧化物歧化酶的影响。两种产生ODFR的系统均受到羟基自由基清除剂的抑制，这表明羟基自由基是这两种系统中直接造成损伤的物质。浓度为1-5 mM的青霉胺可刺激亚铁乙二胺四乙酸螯合物对透明质酸的降解，但抑制XO/HX系统对透明质酸的降解。更高浓度的青霉胺以及所有研究浓度（1-100 mM）的其他抗炎药物（氯喹、硫代苹果酸金钠和水杨酸盐）均抑制自氧化和酶促产生ODFR系统对透明质酸的降解，其抑制效力与已知的羟基自由基清除剂相似。这两种系统均作为ODFR介导的组织损伤的体外模型，这种损伤可能在体内炎症部位发生。
