Iron chelators animal models

Polansky, J. and Weinreb, B. (1984). Anti-inflammatory agents steroids as anti-inflammatory agpnts. In Pharmacology of the Eye (ed. M.L. Sears) pp. 459-538. Springer Verl, Berlin. Rao, N., Romero, J., Fernandez, M. and Marak, G.E. (1986). Effect of iron chelation on severity of occular inflammation in an animal model. Arch. Ophthalmol. 104, 1369-1371. 

Like practically aU living organisms, malaria parasites depend on iron for their growth and replication. This property makes them susceptible to iron deprivation, which can be induced by treatment with iron chelators as shown in in vitro cultures of P. falciparum in animal models of malaria ° and in human trials with... 

Lxtngueville, A., Crichton, R. R. (1986). An animal model of iron overload and its appUcation to study hepatic ferritin iron mobilization by chelators. Biochemical Pharmacology, 35, 3669—3678. 

Evaluation of Iron Chelating Agents Using Animal Models of Iron Overload... 

Prus and Fibach (2012) demonstrated that fermented papaya preparation (FPP) exhibits reactive oxygen species (ROS) scavenging effect on blood cells in both an in vitro and in vivo model (in thalassemic patients and experimental animals). Fermented papaya effectively reduces ROS and it was suggested that its antioxidant mechanism is related, at least in part, to iron chelation. 

While chemical principles can be used to design chelators that form stable and specific Fe chelates, uncertainty about the nature and location of the chelatable iron pool and constraints on delivery of suitable chelators to the site of action have determined that iron chelator design is still dominated by empirical testing of structure-function relationships. This in itself adds a new challenge in that there is no perfect animal model for the human iron overload syndromes. Pitt (1981) has pointed out that rodents Fe-loaded with heat-damaged erythrocytes have been used most frequently to assess the ability of chelators to remove iron by the fecal (biliary) and urinary routes and lower parenchymal (liver) and RES (splenic) stores. He reviews LD50 and iron-removal data on many natural and synthetic hydroxa-mates, phenols, catechols, tropolones, salicylates, benzoates, azines, and carboxylates. No clear picture emerges and the search for the ideal iron chelator continues. 

Blake DR, Hall ND, Bacon PA, Dieppe PA, Halliwell B, Gutteridge JMC (1983) Effect of a specific iron chelating agent on animal models of inflammation. Ann Rheum Dis 42 89-93... 

Assessment of the toxicity of a chelator should in principle be done in an adequate model of the target population of iron-loaded patients. Observations with subjects that lack excessive iron stores may be based on unrealistic concentrations of the uncomplexed chelator, or alternatively show effects of removal of needed baseline iron stores. For example, it is not yet clear whether toxic effects of the hydroxypyridones are an inherent property of the agents themselves, a result of chelation of iron or other trace elements at strategic cellular locations, or a consequence of the mobilization of iron in toxic form. Toxicity of these compounds in animal studies has not been observed to the same extent in significant experience with patients... 

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