Iron retention and excretion in mice transfused with homologous or heterologous blood and treated with chelators.
The studies in this report characterized an animal model for detecting chemicals that are capable of depleting elevated tissue iron. Male mice were transfused with heated, washed erythrocytes and the iron uptake by liver and spleen plus urinary iron excretion were measured. After the time and transfusion iron accumulations and excretion patterns were established, the influence of the following experimental variables was examined and compared: homologous vs heterologous blood transfusion, dose related responses, the efficacy of a chelator against iron buildup from long-term transfusion, and organ iron responses to an agent with combined chelation and hemolytic potentials. Both the liver and the spleen accumulated iron from transfused blood; however, the spleen appeared to have a limited capacity compared to the liver. Drugs having lower potencies or given at lower dose levels enhanced urinary iron excretion. Higher potencies or higher dose levels induced the same response and depleted liver iron. At still higher doses or with more potent drugs, the two responses mentioned occurred accompanied by spleen iron reduction. An increased urine iron alone was equivocal since drug-induced hemolytic anemia caused a ferricosuria accompanied by elevated liver and spleen iron. Heterologous or homologous transfusions produced similar organ iron elevations and urine iron excretion in untreated mice. A higher level of drug potency was required to deplete tissue iron whenever the drug treatment was administered following transfusion.
D000818:Animals; D001803:Blood Transfusion; D002614:Chelating Agents / Q000494:pharmacology*; D006461:Hemolysis; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size; D013154:Spleen / Q000378:metabolism
D002614:Chelating Agents; D007501:Iron