EFFECT OF A SPECIFIC IRON CHELATING AGENT ON ANIMAL-MODELS OF INFLAMMATION
EFFECT OF A SPECIFIC IRON CHELATING AGENT ON ANIMAL-MODELS OF INFLAMMATION
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DOI：
10.1136/ard.42.1.89
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发表时间：
1983-01-01
影响因子：
27.4
通讯作者：
GUTTERIDGE, JMC
中科院分区：
文献类型：
--
作者：
BLAKE, DR;HALL, ND;GUTTERIDGE, JMC
Fe是氧化自由基反应的重要催化剂，促进超氧阴离子自由基和过氧化氢形成羟基自由基。羟基自由基对脂质过氧化的刺激作用促使人们推测游离铁可能直接促进炎症，而铁螯合剂可能具有有用的抗炎特性。这一假设在炎症动物模型中用特定的铁螯合剂去铁胺进行了测试。低剂量（6.6 mg/kg）腹膜内注射去铁胺刺激尿酸钠诱导大鼠急性足垫肿胀，但在较高剂量（高于 200 毫克/千克）时，它会抑制这种炎症反应。在角叉菜胶引起的足垫肿胀中观察到类似的抗炎作用。在用牛丙种球蛋白诱发格林-杜蒙德滑膜炎的豚鼠中，去铁敏（100 mg/kg）刺激了这种慢性过敏性单关节炎模型的急性炎症诱导期。在用牛丙种球蛋白进行关节内攻击后第7-12天重复施用去铁敏（100 mg/kg）可显着抑制慢性炎症阶段。体外实验表明，当 Fe 饱和度较低时，去铁胺可抑制 Fe 催化的脂质过氧化反应，但当 Fe 饱和时，则失去这种作用。这种效应可以解释动物研究中去铁敏的结果，并表明有效的铁螯合及其去除可能会改变人类的炎症过程。
Fe is an important catalyst of oxidative radical reactions and promotes the formation of the hydroxyl radical from the superoxide anion radical and hydrogen peroxide. The stimulatory effect of the hydroxyl radical on lipid peroxidation prompted the speculation that free Fe may directly promote inflammation and that Fe chelating agents may have useful antiinflammatory properties. This hypothesis is tested in animal models of inflammation with a specific Fe chelating agent, desferrioxamine. At low doses (6.6 mg/kg) i.p. desferrioxamine stimulated the induction of acute foot pad swelling in rats by monosodium urate but at higher doses (above 200 mg/kg) it suppressed this inflammatory reaction. A similar antiinflammatory effect was observed in carrageenan-induced foot pad swelling. In guinea pigs in which a Glynn-Dumonde synovitis was induced with bovine gammaglobulin, desferrioxamine (100 mg/kg) stimulated the acute inflammatory induction phase of this chronic allergic monoarthritis model. Repeated administration of desferrioxamine (100 mg/kg) from the 7-12th day after intra-articular challenge with bovine gammaglobulin markedly depressed the chronic inflammatory phase. In vitro experiments suggest that desferrioxamine inhibits Fe-catalyzed lipid peroxidation when it is poorly saturated with Fe, but loses this effect when it is Fe saturated. Such an effect may explain the results with desferrioxamine in the animal studies and suggests that effective Fe chelation and its removal may modify the inflammatory process in man.