Boelaert J R, Van Cutsem J, de Locht M, Schneider Y J, Crichton R R
Unit for Renal and Infectious Diseases, Algemeen Ziekenhuis Sint Jan, Brugge, Belgium.
Kidney Int. 1994 Mar;45(3):667-71. doi: 10.1038/ki.1994.89.
Deferoxamine (DFO), when used in dialysis patients, is a well recognized risk factor for the development of mucormycosis caused by Rhizopus. This study compares, both in vivo and in vitro, the effects produced on Rhizopus by DFO and by two chelators of the hydroxypyridinone class, L1 and CP94. Experimental systemic mucormycosis was induced in the guinea pig by an i.v. injection of two different strains of Rhizopus: R. microsporus and R. arrhizus. Concomitant i.p. administration of DFO for four days shortened animal survival (P < 0.05), whereas concomitant administration of either L1 or CP94 did not. In vitro radioiron uptake by R. microsporus was 100-fold higher from the 55ferric complex of DFO than of L1 or CP94. In vitro fungal growth was stimulated sevenfold by the ferric complex of DFO (P < 0.0001) but not significantly by the ferric complex of either L1 or CP94. These results indicate that the ferric complex of DFO but not that of L1 or CP94 specifically stimulates both the iron uptake and the growth of Rhizopus. They suggest that the risk of developing mucormycosis should be minimal with L1 or CP94, as opposed to DFO.
去铁胺(DFO)用于透析患者时,是由根霉引起的毛霉菌病发生的一个公认风险因素。本研究在体内和体外比较了DFO以及两种羟基吡啶酮类螯合剂L1和CP94对根霉产生的影响。通过静脉注射两种不同的根霉菌株:微小根霉和少根根霉,在豚鼠中诱导实验性系统性毛霉菌病。连续四天腹腔注射DFO会缩短动物存活时间(P < 0.05),而同时注射L1或CP94则不会。体外实验中,微小根霉从DFO的55铁复合物摄取放射性铁的量比从L1或CP94的55铁复合物高100倍。DFO的铁复合物在体外刺激真菌生长达7倍(P < 0.0001),而L1或CP94的铁复合物则无显著刺激作用。这些结果表明,DFO的铁复合物而非L1或CP94的铁复合物能特异性地刺激根霉的铁摄取和生长。这表明与DFO不同,使用L1或CP94时发生毛霉菌病的风险应最小。