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The Effects of Inhibition of Haem Biosynthesis by Griseofulvin on Intestinal Iron Absorption
Author(s) -
Laftah Abas H.,
Raja Kishor B.,
Beaumont Nick,
Simpson Robert J.,
Deacon Allan,
Solanky Nita,
Srai Surjit Kaila S.,
Peters Timothy J.
Publication year - 2004
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2004.pto940402.x
Subject(s) - in vivo , chemistry , griseofulvin , absorption (acoustics) , biochemistry , biosynthesis , porphobilinogen , enzyme , biology , medicine , microbiology and biotechnology , pathology , physics , acoustics
The relationship between haem biosynthesis and intestinal iron absorption in mice was investigated by ascertaining the effect of the haem synthesis inhibitor, griseofulvin, on duodenal iron absorption using both in vivo and in vitro measurements. Urinary 5‐aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3–7 days. Urinary porphobilinogen levels also showed a similar trend. In vivo intestinal iron absorption was significantly reduced (P<0.05) in experimental mice, mainly due to reduction in the transfer of 59 Fe from the enterocytes to the portal circulation. In vitro studies using isolated duodenal fragments also exhibited marked decreases in both iron uptake and Fe (III) reduction. Changes in mucosal Divalent Metal Transporter 1 (DMT‐1), Dcytb and Ireg1 (iron regulated protein 1) mRNA levels paralleled the changes in iron absorption. The reduction in iron absorption after griseofulvin treatment was normalised when mice were simultaneously injected with haem‐arginate. These data support the hypothesis that intermediates in haem biosynthesis, particularly 5‐aminolaevulinic acid, regulate intestinal iron absorption.