Modulation of duodenal iron uptake by hypoxia and fasting in the rat

The effect of hypoxic exposure on in vho duodenal Fe uptake kinetics was studied in tissue fragments from rats that were fed or fasted overnight before study. Hypoxic exposure was for 3 d at 0.5 atm and fasting was for the last 18-24 h before Fe uptake determinations. The non-permeable Fezʹ chelator 3-(2pyridyl)-5,6-bis-(~phenyl-sulpho~acc id)-l,2,4triazine (ferrozine), and medium deoxygenation inhibited uptake in all experimental groups. Ferrozine sensitivity and mucosal Fe3+ reductase activity were greatest in hypoxic animals. Fe uptake was inhibited by membrane depolarization only after fasting or hypoxic exposure of the rats. The data demonstrated that Fe uptake by rat duodenal fragments involves at least two mechanisms: a membrane-potentialindependent mechanism which is not responsive to hypoxia and a second mechanism, induced by fasting or hypoxia, which is inhibited by membrane depolarization. Uptake is partially dependent on reduction of Fe3+ to Fez+ and this is primarily associated with the second mechanism for uptake. These properties have been reported also in mouse and human Fe uptake, suggesting that the rat is a useful model for the study of basic mechanisms of Fe absorption.