Lurie Ziva, Offer Tal, Russo Angelo, Samuni Amram, Nitzan Dorrit
Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Free Radic Biol Med. 2003 Jul 15;35(2):169-78. doi: 10.1016/s0891-5849(03)00270-3.
Reactive oxygen-derived species and particularly OH radicals can degrade hyaluronic acid (HA), resulting in a loss of viscosity and a subsequent decrease in its effectiveness as a joint-lubricating agent. The production of OH in the vicinity of HA can be catalyzed by bound redox-active metals, which participate in the Haber-Weiss reaction. Damage to HA can also occur as a result of hypochlorite formed by myeloperoxidase (MPO). The protective reagents commonly used to inhibit oxidative stress-induced degradation of HA include antioxidative enzymes, such as SOD and catalase, chelators that coordinate metal ions rendering them redox-inactive, and scavengers of radicals, such as OH, as well as nonradical reactive species. In recent years, stable cyclic nitroxides have also been widely used as effective antioxidants. In many cases, nitroxide antioxidants operate catalytically and mediate their protective effect through an exchange between their oxidized and reduced forms. It was anticipated, therefore, that nitroxides would protect HA from oxidative degradation as well. On the other hand, nitroxides serve as catalysts in many oxidation reactions of alcohols, sugars and polysaccharides, including hyalouronan. Such opposite effects of nitroxides on oxidative degradation are particularly intriguing and the aim of the present study was to examine their effect on HA when subjected to diverse forms of oxidative stress. The results indicate that nitroxides protect HA from OH radicals generated enzymatically or radiolytically. The protective effect is attributable neither to the scavenging of OH nor to the oxidation of reduced metal, but to the reaction of nitroxides with secondary carbohydrate radicals-most likely peroxyl radicals.
活性氧衍生物种，特别是羟基自由基，可以降解透明质酸（HA），导致其粘度丧失，并随后降低其作为关节润滑剂的有效性。HA附近羟基的产生可由结合的氧化还原活性金属催化，这些金属参与哈伯-维伊斯反应。由髓过氧化物酶（MPO）形成的次氯酸盐也会导致HA的损伤。通常用于抑制氧化应激诱导的HA降解的保护试剂包括抗氧化酶，如超氧化物歧化酶（SOD）和过氧化氢酶，能使金属离子配位从而使其失去氧化还原活性的螯合剂，以及自由基清除剂，如羟基自由基，还有非自由基反应性物种。近年来，稳定的环状氮氧化物也被广泛用作有效的抗氧化剂。在许多情况下，氮氧化物抗氧化剂具有催化作用，并通过其氧化态和还原态之间的交换来介导其保护作用。因此，可以预期氮氧化物也能保护HA免受氧化降解。另一方面，氮氧化物在醇、糖和多糖（包括透明质酸）的许多氧化反应中起催化剂的作用。氮氧化物对氧化降解的这种相反作用特别令人感兴趣，本研究的目的是研究它们在受到多种形式的氧化应激时对HA的影响。结果表明，氮氧化物可保护HA免受酶促或辐射产生的羟基自由基的损伤。这种保护作用既不是由于羟基自由基的清除，也不是由于还原态金属的氧化，而是由于氮氧化物与二级碳水化合物自由基（最有可能是过氧自由基）的反应。
