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Marginally excessive iron loading transiently blocks mucosal iron uptake in iron-deficient rats
Shoko Shinoda1, Shiho Yoshizawa2, Eriko Nozaki2
1Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo, Japan; and sshinoda@tmu.ac.jp.
Abstract:
Regular "mucosal block" is characterized by decreased uptake of a normal iron load 3-72 h after the administration of excess iron (generally 10 mg) to iron-deficient animals. We found that short-acting mucosal block could be induced by much lower iron concentration and much shorter induction time than previously reported, without affecting levels of gene expression. A rapid endocytic mechanism was reported to decrease intestinal iron absorption after a high iron load, but the activating iron load and the time to decreased absorption were undetermined. We assessed the effects of 30-2,000 μg iron load on iron uptake in the duodenal loop of iron-deficient and iron-sufficient rats under anesthesia. One hour later, mucosal cellular iron uptake in iron-deficient rats administered 30 μg iron was 76.1%, decreasing 25% to 50.7% in rats administered 2,000 μg iron. In contrast, iron uptake by iron-sufficient rats was 63% (range 60.3-65.5%) regardless of iron load. Duodenal mucosal iron concentration was significantly lower in iron-deficient than in iron-sufficient rats. Iron levels in portal blood were consistently higher in iron-deficient rats regardless of iron load, in contrast to the decreased iron uptake on the luminal side. Iron loading blocked mucosal uptake of marginally excess iron (1,000 μg), with a greater effect at 15 min than at 30 min. The rapid induction of short-acting mucosal block only in iron-deficient rats suggests DMT1 internalization.
Insights
Iron overload triggers a rapid "mucosal block" in iron-deficient rats, significantly reducing iron absorption. This short-acting mechanism, observed with lower iron loads than previously thought, suggests DMT1 internalization.
Area of Science:
- Physiology
- Gastroenterology
- Nutritional Science
Background:
- The intestinal
- mucosal block
- regulates iron absorption, typically occurring 3-72 hours after high iron intake in iron-deficient animals.
Purpose of the Study:
- To investigate the iron load and time course required to induce a short-acting mucosal block in iron absorption.
- To determine if this block is specific to iron-deficient states and elucidate the underlying mechanism.
Main Methods:
- Assessed iron uptake in the duodenal loop of anesthetized iron-deficient and iron-sufficient rats after administration of varying iron loads (30-2,000 μg).
- Measured mucosal cellular iron uptake, duodenal mucosal iron concentration, and iron levels in portal blood at different time points (15, 30, and 60 minutes).
Main Results:
- A significant decrease in mucosal iron uptake was observed in iron-deficient rats with iron loads as low as 30 μg, with uptake decreasing from 76.1% to 50.7% as the load increased to 2,000 μg.
- Iron-sufficient rats showed consistent iron uptake (around 63%) irrespective of the iron load.
- Iron loading blocked uptake of 1,000 μg iron more effectively at 15 minutes than 30 minutes, indicating rapid induction.
Conclusions:
- Short-acting mucosal block can be induced by lower iron concentrations and shorter induction times than previously reported, specifically in iron-deficient rats.
- The rapid onset and iron-deficiency specificity suggest the internalization of the divalent metal transporter 1 (DMT1) is the primary mechanism.
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