Rat Intestinal Iron Transfer Capacity and the Longitudinal Distribution of Its Adaptation to Iron Deficiency

Abstract

The longitudinal gradient of intestinal iron transfer was investigated in normal and iron-deficient male Sprague-Dawley rats in vitro and in vivo. In normal rats in vitro iron transfer in the duodenum was approximately 3 times higher than in the jejunum and decreased in the ileum to approximately half the jejunal values. Compared to the controls in vitro iron transfer was increased 3–4 times in the duodenum and in the first jejunal segment and 2–3 times in the second jejunal segment. No significant adaptation to iron deficiency was found in the rest of the small intestine. Iron transfer rates showed the same longitudinal pattern when iron was chelated with nitrilotriacetic acid (NTA) or with ascorbate. The absorbed iron quantities, however, were approximately 5 times lower when Fe-ascorbate was used, which might be due to differences in bioavailability. Omission of Fe-NTA and Fe-ascorbate had no impact on the vitality of the segments. Glucose transfer was used as vitality criterion. It was not significantly different between corresponding iron-deficient and control segments. To control these results in vivo mesenteric blood was collected from duodenal and jejunal segments in situ. Corresponding to in vitro findings iron transfer was close to linear over the experimental period. In iron deficient duodenal segments iron transfer increased approximately 3 times as compared to controls while no adaptational changes were found in the distal jejunum. No significant longitudinal gradient was found in the mucosal content of ferritin and nonheme iron. Both parameters were decreased in iron deficiency by about half. The mucosal transferrin content showed no longitudinal gradient in control animals. In iron deficiency transferrin was significantly increased in the duodenum and in the three most proximal jejunal segments. The results indicate that in rats adaptation of iron absorption to the demand can only be expected in the duodenum and in the proximal 20 cm of the jejunum. Because this process shows a steep gradient in the proximal small intestine, studies on the adaptation of intestinal iron transfer to the demand should use short and well-defined segments in order to provide reproducible results.

Iron regulatory protein as an endogenous sensor of iron in rat intestinal mucosa

“…This parameter as well as constant transport rates for water and 59 Fe were used to continuously monitor ex-vivo viability. Duodenal transfer rates for 59 Fe and 109 Cd as determined by this method were in the same order of magnitude or even identical to corresponding transfer rates determined in vivo [7,36].…”

“…The ability to adapt intestinal iron absorption capacity to different states of iron repletion is restricted to the proximal small intestine [7,8]. IRP-1 activity in the mucosal cells at the villus tips and duodenal iron absorption from the lumen show parallel changes in iron deficiency (Table 3), which suggests that IRP may be involved in the adaptation of intestinal iron absorption to changes in body iron requirements.…”

Characteristics of Iron Binding to Solubilized Brush Border Membrane of the Rat Intestine.

“…This finding is consistent with the fact that iron absorption mainly occurs in the duodenum (1,6,36) and suggests that the low-affinity sites might be important in iron absorption .…”

Toxicological overview of a novel strobilurin fungicide, orysastrobin

“…Studies in which rats were treated with an iron-deficient diet have shown that this treatment results in similar duodenal changes. [1][2][3] A mechanistic study in mice also established increased proliferation of the epithelium of duodenal mucosa after 4 weeks at the carcinogenic dose of 2000 ppm, demonstrating that the same mechanism occurs in this species.…”