Abstract
The present study aimed to demonstrate that Sideral® RM (SRM, Sucrosomial® Raw Material Iron) is transported across the excised intestine via a biological mechanism, and to investigate the effect that this transport route may produce on oral iron absorption, which is expected to reduce the gastrointestinal (GI) side effects caused by the bioavailability of non-absorbed iron. Excised rat intestine was exposed to fluorescein isothiocyanate (FITC)-labeled SRM in Ussing chambers followed by confocal laser scanning microscopy to look for the presence of fluorescein-tagged vesicles of the FITC-labeled SRM. To identify FITC-labeled SRM internalizing cells, an immunofluorescence analysis for macrophages and M cells was performed using specific antibodies. Microscopy analysis revealed the presence of fluorescein positive particulate structures in tissues treated with FITC-labeled SRM. These structures do not disintegrate during transit, and concentrate in macrophage cells. Iron bioavailability was assessed by determining the time-course of Fe3+ plasma levels. As references, iron contents in liver, spleen, and bone marrow were determined in healthy rats treated by gavage with SRM or ferric pyrophosphate salt (FP). SRM significantly increased both area under the curve (AUC) and clearance maxima (Cmax) compared to FP, thus increasing iron bioavailability (AUCrel = 1.8). This led to increased iron availability in the bone marrow at 5 h after single dose gavage.
Highlights
Iron deficiency is one of the most widespread nutritional deficiencies [1]
Ex vivo experiments showed that when SRM comes into contact with aqueous fluids, it extemporaneously forms vesicular-like structures that are internalized by epithelial cells
The studies with the confocal laser scanning microscope clarified that these vesicles remain intact during transit through the entire tissue, while the immunofluorescence studies showed that these vesicles, once internalized by epithelial cells, are concentrated in macrophages
Summary
Iron deficiency is one of the most widespread nutritional deficiencies [1]. Oral supplementation of iron deficiency is mainly based on ferrous iron formulations [2]. Numerous gastrointestinal side effects, including an increased risk of intestinal inflammation, constipation, and diarrhea, affecting the microbiota, have been reported [3,4,5,6,7,8]. Despite its crucial role in cellular processes, the presence of free iron can generate toxic free radicals and oxygen reactive species, which can impair the integrity of intestinal epithelium by promoting redox stress [10]. Such a compromised integrity was indicated by in vitro studies on Caco-2 cells exposed to iron [11,12]. To enhance the absorption of administered iron, and at the same time ruling out gastrointestinal (GI)
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