Role of kidneys in heme detoxification and iron metabolism during neonatal jaundice – research based on laboratory mouse model

Neonatal jaundice (neonatal hyperbilirubinemia) is a physiological process caused by degradation of foetal erythrocytes. In humans, it starts in the second day of life and finishes at about day 10. During this short period in the organism of neonate large amounts of bilirubin – product of heme decay are generated as an effect of haemolysis of foetal erythrocytes. Because of impaired bilirubin clearance, excess of this compound circulates in the body, infiltrates to the skin and mucosa, giving them characteristic, yellow colour. Accumulation of unconjugated bilirubin is highly toxic, because this compound can diffuse through blood-brain barrier and cause damage of brain structures, especially the basal nuclei. According to the present knowledge, liver and spleen are the main organs, which participate in clearance of haemoglobin degradation products formed during haemolysis. In this project we show that also kidneys are involved in the process of heme detoxification and iron utilization in neonatal individuals. In our study we used 3, 5, 7, 9 and 11 day-old male mice as a mammalian model organisms. To confirm that tested animals undergo neonatal jaundice and haemolysis we measured bilirubin, haptoglobin and hemopexin levels in plasma. Kidneys were analysed for a wide panel of proteins involved in iron metabolism, including iron importers (DMT1, TfR1), heme transporters (HCP1, HRG1, FLVCR2), heme oxygenase 1 and 2 (HO-1, HO-2) and ferroportin (FPN), iron exporter. In this study we report that heme and iron transporters and heme oxygenase 1 are highly expressed in the cells of the renal tubules. Our results suggest that kidneys may play an important role in postpartum iron recirculation when the metabolism of this element depends primarily on iron stored in the liver.