Mechanisms and Regulation of Intestinal Iron Absorption

Peters, Timothy J.; Raja, Kishor B.; Simpson, Robert J.; Snape, Sue

doi:10.1111/j.1749-6632.1988.tb55500.x

Cited by 38 publications

(10 citation statements)

References 40 publications

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“…It is well known that iron absorption decreases when body iron stores are raised and increases during periods of iron deficiency and that these alterations are effected by mechanisms within the duodenum (Forth & Rummel, 1973 alterations in demand e.g. via erythropoeisis modifying iron transfer from serosal surface to plasma but also changes taking place at the luminal surface of the duodenum modifying initial uptake (Muir & Hopfer, 1985;Raja et al, 1988). In the present study, significantly lower rates of iron uptake from ferric maltol were observed in duodenal fragments compared with ileal fragments isolated from animals pretreated for two weeks with ferric maltol.…”

Section: Discussionmentioning

confidence: 99%

Evidence for regulatory control of iron uptake from ferric maltol across the small intestine of the rat

Barrand

Callingham

1991

British J Pharmacology

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159Fe absorption from the novel iron compound, ferric maltol, was studied in rats pretreated twice daily for two weeks with non-radioactive ferric maltol in oral doses containing 7 mg elemental iron. Tissue accumulation of 59Fe 2 h after administration of radioactive ferric maltol into the stomach was significantly lower in iron pretreated animals than in saline-treated controls. 2 59Fe uptake from ferric maltol into isolated fragments of ileum and of duodenum was of similar magnitude in control animals but in iron-treated animals, duodenal uptake was significantly lower than that of the ileum. 3 Absorption of 59Fe was also investigated in anaesthetized rats after intestinal perfusion with saline (controls) or with 5 mm chenodeoxycholate to render the intestines more permeable. 4 Changes in permeability of the small intestine were monitored by estimating the amount of ['4C]-mannitol absorbed and fluid secreted with reference to the non-absorbable [3H]-inulin in the perfusate effluents.

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Section: Discussionmentioning

confidence: 99%

Evidence for regulatory control of iron uptake from ferric maltol across the small intestine of the rat

Barrand

Callingham

1991

British J Pharmacology

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“…It has already been established that at low doses of ferric maltol much of the iron absorbed into the intestinal mucosa of iron replete animals becomes associated with ferritin Levey et al, 1988;Barrand & Callingham, 1991). Transfer of iron from the serosal surface to transferrin in the circulation will then be regulated by the demands for iron in the peripheral tissues (Peters et al, 1988) and may well take place as a slow release. At high doses, dissociation of metal and ligand may be very slow, hence the slow entry of maltol into the circulation.…”

Section: Discussionmentioning

confidence: 99%

Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat

Barrand

Callingham

Dobbin

et al. 1991

British J Pharmacology

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I The fate and disposition of [59Fe]-ferric [3H]-maltol after intravenous administration were investigated in anaesthetized rats. Immediate dissociation of ferric iron from maltol took place in the circulation even with high doses of ferric maltol (containing 1 mg elemental iron). In plasma samples withdrawn within 1 min of injection and subjected to gel filtration, 59Fe eluted with the high molecular weight proteins whilst the tritium was associated with low molecular weight material. 2 The rates of elimination of 59Fe and of tritium from the plasma and their ultimate fate were very different. The half life for "Fe in the plasma was around 70min and "Fe appeared mainly in the bone marrow and liver. There was an initial rapid exit of tritium from the plasma with a half life of around 12min. This was followed either by a plateau or by a rise in tritium levels, involving entry of maltol metabolites into the circulation. These metabolites could be recovered in the urine.3 Entry of "Fe and of tritium into the blood plasma after intraduodenal administration of [59Fe]-ferric [3H]-maltol was also very different. At low doses of ferric maltol (containing 100,ug elemental iron), the tritium appeared in the plasma in highest amounts within seconds and then decreased whilst there was a slow rise in "Fe levels. At higher doses of ferric maltol (containing 7 mg elemental iron), levels of "Fe in the plasma were highest at 5 min and then fell whereas tritium levels rose steadily. Mucosal processing of 59Fe prevented further entry of iron at high dose into the circulation. 4 Initial rates of uptake of [3H]-maltol into isolatcd intestinal fragments were measured over a range of concentrations and revealed that maltol alone could diffuse freely into the tissues whereas maltol complexed to iron showed saturable uptake kinetics similar to those seen with the iron itself. 5 After intestinal uptake, 59Fe and tritium were associated with different subcellular fractions, maltol itself being metabolized to the glucuronide conjugate within the intestinal mucosa. 6 It is concluded that dissociation of metal and ligand takes place before entry into the intestinal mucosa. Iron is then taken up on the endogenous carrier and processed in the normal way whilst maltol enters by diffusion, its rate of entry being limited by the degree of dissociation. It is subsequently metabolized by conjugation and eliminated rapidly from the body in the urine. IntroductionIt is generally supposed that ferrous preparations are more effective in the oral treatment of iron deficiency than ferric compounds partly at least because of the low bioavailability of ferric iron (Dietzfelbinger, 1987). Ferrous preparations may cause irritation and damage to the mucosal lining, particularly in overdose (Nayfield et al., 1976). Thus compounds that can hold ferric iron in absorbable form might be a therapeutic advantage. The hydroxypyrone, maltol, has a very high affinity for ferric iron (Kaff value of ferric iron for maltol of log fl3 = 28) and appears able to hold the me...

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“…Another [43] found that the fatty acids bound Fe(II). We have favoured the ferrous state because iron uptake correlates with the hepatocyte membrane's redox activity, and also because iron uptake is inhibited by divalent cations of ionic radii similar to that of ferrous iron [29,36].…”

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

The role of transferrin in the mechanism of cellular iron uptake

Thorstensen

Romslo

1990

Biochemical Journal

185

106

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INTRODUCTIONThe role of transferrin and its cell surface receptor in cellular iron metabolism has received considerable interest during the last decade. Hence, over this period several reviews covering various aspects of the topic have been published.In this review we attempt to summarize the new knowledge and controversies encountered during the last 4-5 years. The focus is on iron metabolism by the hepatocyte. We also view the concept of transferrin-cell interactions from angles which previously may not have been given particular attention, and we include some aspects of iron metabolism not normally covered by reviews of this type. Central parts of what may be regarded as well-established knowledge either have been entirely omitted, or are only briefly described or mentioned to the extent considered relevant to the particular topic discussed. Important aspects of iron metabolism such as iron adsorption, haemochromatosis, ferritin iron and iron in infection and neoplasia are not covered in the present paper. Instead, the reader is referred to one or more of the recently published reviews [1-5] and references therein.

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Mechanisms and Regulation of Intestinal Iron Absorption

Cited by 38 publications

References 40 publications

Evidence for regulatory control of iron uptake from ferric maltol across the small intestine of the rat

Evidence for regulatory control of iron uptake from ferric maltol across the small intestine of the rat

Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat

The role of transferrin in the mechanism of cellular iron uptake

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