Tissue-specific changes in iron metabolism genes in mice following phenylhydrazine-induced haemolysis

Iron metabolism in animals is altered by haemolytic anaemia induced by phenylhydrazine (PHZ). In common with a number of other modulators of iron metabolism, the mode and the mechanisms of this response are yet to be determined. However, recent studies have shown increased expression of the ferrous transporter DMT1 in the duodenum and other tissues of mice administered PHZ. We examined the expression of the ferric reductase Dcytb, DMT1 and some other genes involved in Fe metabolism in tissues of mice dosed with PHZ. The expression of iron-related genes in the duodenum, liver, and spleen of the mice were evaluated using Northern blot analyses, RT-PCR and immunocytochemistry. Dcytb, and DMT1 mRNA and protein increased markedly in the duodenum of mice given PHZ. The efflux protein Ireg1 also increased in the duodenum of the treated mice. These changes correlated with a decrease in hepatic hepcidin expression. Dcytb, DMT1, Ireg1 and transferrin receptor 1 mRNA expression in the spleen and liver of mice treated with PHZ responded to the enhanced iron demand associated with the resulting stimulation of erythropoiesis. Enhanced iron absorption observed in PHZ-treated animals is facilitated by the up-regulation of the genes involved in iron transport and recycling. The probable association of the erythroid and the store regulators of iron homeostasis and absorption in the mice is discussed.