Two mouse models of hemosiderosis are compared. Increased deposition of iron in internal organs is confirmed histochemically. The effectiveness of desferal therapy is evaluated by urinary excretion of iron.
Key Words: hemosiderosis; histochemistry; desferalProblems associated with the treatment of hemosiderosis and hemochromatosis have not been solved. Therefore, the development of effective therapeutic and preventive measures is very important. Desferal, an agent binding and eliminating excessive iron, has been used in clinical practice for more that two decades [4]. However, this preparation has a number of serious disadvantages [2,9,10,11], so the need for safe and effective drugs still remains. A great number of models for the investigation of iron chelators has been developed [3,5,8]. The search for new chelating agents [1] implies the evaluation of effectiveness of potential drugs. We think that the model proposed by C. G. Pitt [7] --induction of hemosiderosis in mice by injection of heterogenic erythrocytes --is one of the most convenient.Our objective was to compare two mouse models of hemosiderosis: the model developed by Pitt and our model, in which hemosiderosis was initiated by injection of allogenic erythrocytes.
MATERIALS AND METHODSExperiments were performed on 100 outbred albino mice of both sexes weighing 20-23 g. The animalsHematology Research Center, Russian Academy of Medical Sciences, "-Moscow were divided into equal groups. Group I mice (n = 50) were intraperitoneally injected with human packed erythrocytes by the method of Pitt. Group II mice (n=50) were intraperitoneally injected with packed erythrocytes of outbred albino mice. In both groups erythrocytes were injected in doses 0.25, 0.5, and 1.0 ml during a 4-day period. Half of mice in each group were treated with desferal (daily dose 0.5 ml per animal), and the other half mice were injected with normal saline. The mice were decapitated before and at different periods of desferal or normal saline treatment. The effectiveness of treatment was evaluated from the content of iron in the urine and by histochemical methods. The urine was collected during a 4-day period after administration of desferal using replaceable cages. The urinary content of iron was determined by the method of [6] with our modifications. The intensity of hemosiderosis in internal organs was assessed by the histochemical method of Perls after fixation in neutral Formalin and embedding in paraffin.
RESULTSAdministration of human packed erythrocytes to mice in a dose of 0.25 ml per animal resulted in the development of prolonged (1 month) hemosiderosis of internal organs, which was particularly