title: Effect of Tin-mesoporphyrin, an inhibitor of haem catabolism, on intestinal iron absorption.
abstract: Haem biosynthesis is the most important destination for absorbed iron, hence it can be hypothesized that iron absorption regulation should be integrated with haem metabolism. As an initial step to test this hypothesis, the effect on iron absorption of Tin-mesoporphyrin (SnMP), inhibitor of haem oxygenase, altering haem and its biosynthetic intermediates, was studied. Mice injected with SnMP (5-25 micro mol/kg daily for up to 3 d) showed dose-dependent increases in intestinal iron absorption measured in vivo and in vitro. In order to investigate the effects of SnMP, enzymes and intermediates of haem metabolism were measured. Hepatic 5-amino-laevulinate (ALA) synthase activity (pmol/min/mg protein) was significantly reduced in SnMP-treated mice (10 and 25 micro mol/kg daily for 3 d) (mean +/- standard deviation, control 11.2 +/- 2.6; treated 6.3 +/- 1.7; P < 0.01). Hepatic ALA dehydratase activity (pmol porphobilinogen/mg protein/min) showed significant reductions following SnMP treatment (control 180 +/- 60, treated 130 +/- 50; P < 0.05). The effect of SnMP on iron absorption was reversible, with absorption returning to normal after 3 d. Furthermore, the effect of SnMP on duodenal iron absorption was abolished by the simultaneous injection of ALA (6 micro mol/l). ALA alone had no effect on iron absorption. In-vitro studies using duodenal fragments isolated from mice treated with SnMP (10 micro mol/kg daily for 3 d), showed significant increases (P < 0.05) in both mucosal iron uptake and Fe(III) reducing activity. We conclude that intermediates in haem metabolism, in particular levels of ALA, may play a role in duodenal iron absorption.
authors.affiliation: Department of Clinical Biochemistry, GKT School of Medicine and Dentistry Department of Life Sciences, King's College London, London, UK. abas.h.laftah@kcl.ac.uk
authors.forename: Abas H
authors.initials: AH
authors.lastname: Laftah
authors.forename: Kishor
authors.initials: K
authors.lastname: Raja
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Peters
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000652:urine; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D007408:Intestinal Absorption / Q000187:drug effects*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D000622:Aminolevulinic Acid; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase