Hicks M, Wong L S, Day R O
Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Free Radic Res Commun. 1993;18(6):337-51. doi: 10.3109/10715769309147501.
The aim of the present study was to separate and characterise products formed by oxidation of uric acid by hydroxyl radicals with a view to probing for these products in vivo in clinical contexts. Aerated solutions of 200 microM uric acid, or its oxidation products, allantoin or parabanic acid, were exposed to gamma radiolysis, (52.0 Gy/min), as a source of HO. radicals, at pH 3.4 and 7.4. Aliquots were taken every 5 minutes for 20 minutes and oxidation products were separated by HPLC and analysed with a diode array detector. Identities of oxidation products were confirmed on the basis of similarity of retention times and absorbance spectra and peak purity parameters of known standards. Hydroperoxides were measured by tri-iodide formation in the 20 minute sample. Exposure of uric acid to such HO.fluxes produced a net loss of the parent compound with formation of a complex mixture of products with allantoin and parabanic acid being the predominant products at pH 3.4. The rate of uric acid degradation at physiological pH was slower and the distribution of oxidation products was different. A small but significant amount of uric acid hydroperoxide was detected at both pHs. A mechanism for uric acid oxidation under these conditions is presented.
本研究的目的是分离和表征尿酸被羟基自由基氧化形成的产物，以便在临床环境中对体内的这些产物进行探测。将200微摩尔尿酸的曝气溶液或其氧化产物尿囊素或脲基甲酸暴露于γ辐射分解（52.0戈瑞/分钟），作为羟基自由基的来源，pH值分别为3.4和7.4。每隔5分钟取一次等分试样，共取20分钟，氧化产物通过高效液相色谱分离，并用二极管阵列检测器进行分析。根据已知标准品的保留时间、吸收光谱和峰纯度参数的相似性来确认氧化产物的身份。通过在20分钟的样品中形成三碘化物来测量过氧化氢。尿酸暴露于这种羟基自由基通量下会导致母体化合物净损失，形成复杂的产物混合物，在pH值为3.4时，尿囊素和脲基甲酸是主要产物。在生理pH值下尿酸的降解速度较慢，氧化产物的分布也不同。在两个pH值下均检测到少量但显著量的尿酸过氧化氢。本文提出了在这些条件下尿酸氧化的机制。
