Cantin-Esnault D, Richard J M, Jeunet A
Groupe GEDEXE, UFR de Pharmacie de Grenoble, La Tronche, France.
Free Radic Res. 1998 Jan;28(1):45-58. doi: 10.3109/10715769809097875.
Orellanine, [2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide, is the toxin responsible for the lethal nephrotoxicity of some Cortinarius mushrooms. Our present ESR and spin-trapping studies of the redox properties of the system of non-illuminated orellanine, ferrous iron and dioxygen contribute to understanding the molecular mechanism of its toxicity. UV-visible spectrophotometry, cyclic voltammetry and ESR in frozen medium showed the formation of a wine-red tris complex, Fe(III)Or3. This ferric complex is easily reducible (Ep = -565 mV vs Ag/AgCl/3M KCl at pH 7), involving a one-electron reversible process. Spin-trapping using DMPO is employed to detect the generation of superoxide anion and hydroxyl radicals. The instantaneous one-electron oxidation of ferrous ions in the presence of the toxin under air is concomitant with dioxygen consumption as supported by dioxygen consumption. GSH involves the toxin and ferrous ions under air in a redox cycling process resulting in the production of glutathionyl and oxygen free radicals, observed for the first time with an iron complex of a mushroom toxin. In most cases, EDTA is not able to prevent the Fe(III)Or3 and radical formation. The ortho-dihydroxylated groups borne by the di-N-oxidized bipyridine structure and not the bipyridine structure itself, are responsible for the formation of a stable ferric complex at pH 7, as they are for the generation of an apparently stable ortho-semiquinone anion radical. These one-electron mechanisms may play a major role in some of the known toxic effects of orellanine.
奥来毒素，即[2,2'-联吡啶]-3,3',4,4'-四醇-1,1'-二氧化物，是某些丝膜菌属蘑菇具有致死性肾毒性的毒素。我们目前对未受光照的奥来毒素、亚铁离子和氧气体系的氧化还原特性进行的电子自旋共振（ESR）和自旋捕获研究，有助于理解其毒性的分子机制。紫外可见分光光度法、循环伏安法以及冷冻介质中的ESR表明形成了酒红色的三配合物Fe(III)Or3。这种铁配合物易于还原（在pH 7时相对于Ag/AgCl/3M KCl，Ep = -565 mV），涉及单电子可逆过程。使用二甲基吡啶氧化物（DMPO）进行自旋捕获以检测超氧阴离子和羟基自由基的产生。在空气中毒素存在的情况下亚铁离子的瞬时单电子氧化伴随着氧气消耗，这一点得到了氧气消耗实验的支持。谷胱甘肽（GSH）在空气中使毒素和亚铁离子参与氧化还原循环过程，导致谷胱甘肽基和氧自由基的产生，这是首次在蘑菇毒素的铁配合物中观察到。在大多数情况下，乙二胺四乙酸（EDTA）无法阻止Fe(III)Or3和自由基的形成。由二-N-氧化联吡啶结构而非联吡啶结构本身所携带的邻二羟基基团，在pH 7时负责形成稳定的铁配合物，就如同它们负责生成明显稳定的邻半醌阴离子自由基一样。这些单电子机制可能在奥来毒素的一些已知毒性作用中起主要作用。
