Symons Andrew M, King Laurence J
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
Inflammopharmacology. 2003;11(1):75-86. doi: 10.1163/156856003321547121.
Inflammation may ultimately result from damage to membrane lipids by reactive oxygen species (ROS) such as peroxide, superoxide anion, hydroxyl radical and singlet oxygen. This study compares some of the methods used to determine ROS-ethane exhalation, malondialdehyde quantified as thiobarbituric acid-reacting materials, and luminol-activated chemiluminescence (LAC)-and explores possible relationships with oedema formation in the rat foot-pad model. Iron nitrilotriacetate was the most effective of the model compounds tested in producing lipid peroxidation and ethane exhalation in mice. In the mouse and the rat, iron nitrilotriacetate caused increased ethane exhalation and concomitant increases in liver and kidney malondialdehyde. In the rat foot-pad oedema model, the challenge with Freund's complete adjuvant produced maximum malondialdehyde and maximum LAC in the inflamed paw 8 h after dosing, at which time oedema had also reached a high level. These effects were attributed mainly to hydroxyl radical and singlet oxygen. The inhibition of oedema by four anti-inflammatory drugs correlated well with LAC but less well with inhibition of malondialdehyde production. This study shows good agreement between different methods of determining ROS formation, and that inhibition of ROS formation in vivo is paralleled by a decrease in inflammation.
炎症最终可能源于活性氧（ROS）如过氧化物、超氧阴离子、羟基自由基和单线态氧对膜脂质的损伤。本研究比较了一些用于测定ROS的方法——乙烷呼出量、以硫代巴比妥酸反应物质定量的丙二醛，以及鲁米诺激活的化学发光（LAC）——并探讨了在大鼠足垫模型中与水肿形成的可能关系。在诱导小鼠脂质过氧化和乙烷呼出方面，次氮基三乙酸铁是所测试的模型化合物中最有效的。在小鼠和大鼠中，次氮基三乙酸铁导致乙烷呼出增加，同时肝脏和肾脏中的丙二醛也增加。在大鼠足垫水肿模型中，用弗氏完全佐剂攻击后，给药8小时时炎症爪中的丙二醛和LAC达到最大值，此时水肿也达到高水平。这些效应主要归因于羟基自由基和单线态氧。四种抗炎药对水肿的抑制作用与LAC相关性良好，但与丙二醛生成的抑制相关性较差。本研究表明，不同的ROS形成测定方法之间具有良好的一致性，并且体内ROS形成的抑制与炎症的减轻平行。
