Ferrous bisglycinate increased iron transportation through DMT1 and PepT1 in pig intestinal epithelial cells compared with ferrous sulphate

Liao, Zh.-Ch.; Guan, Wutai; Chen, F.; Hou, Defu; Wang, Ch.-X.; Lv, Yantao; Qiao, Hanzhen; Chen, J.; Han, Jingluan

doi:10.22358/jafs/65704/2014

Cited by 9 publications

(8 citation statements)

References 34 publications

(36 reference statements)

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“…In addition, we also measured the expression of intestinal peptide transporter PepT1. A previous study reported that Fe-Gly significantly increases PepT1 mRNA level and protein expression in the small intestinal epithelium cells (IPEC-1) of pigs, and the reporter thought that Fe-Gly may be mediated into the intestinal cells via PepT1 [15]. However, in our study, the expression of PepT1 did not differ between wild-type and DMT1-knockout cells and between Fe-Gly and FeSO 4 treatment (Figure 5E).…”

Section: Discussioncontrasting

confidence: 62%

“…Their studies have shown that the intestinal uptake of amino acid chelated iron was in greater amounts and more rapid than equivalent quantities of iron salts. Furthermore, compared with FeSO 4 , Fe-Gly has been shown to significantly increase PepT1 mRNA level and protein expression in the small intestinal epithelium cells (IPEC-1) of pigs [14,15]. Others thought that amino acid chelated iron was absorbed by the enterocytes in the same manner as inorganic iron.…”

Section: Introductionmentioning

confidence: 99%

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Iron Transport from Ferrous Bisglycinate and Ferrous Sulfate in DMT1-Knockout Human Intestinal Caco-2 Cells

Chen

Ding

et al. 2019

Nutrients

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This experiment was conducted to investigate the transport characteristics of iron from ferrous bisglycinate (Fe-Gly) in intestinal cells. The divalent metal transporter 1 (DMT1)-knockout Caco-2 cell line was developed by Crispr-Cas9, and then the cells were treated with ferrous sulfate (FeSO4) or Fe-Gly to observe the labile iron pool and determine their iron transport. The results showed that the intracellular labile iron increased significantly with Fe-Gly or FeSO4 treatment, and this phenomenon was evident over a wide range of time and iron concentrations in the wild-type cells, whereas in the knockout cells it increased only after processing with high concentrations of iron for a long time (p < 0.05). DMT1-knockout suppressed the synthesis of ferritin and inhibited the response of iron regulatory protein 1 (IRP-1) and IRP-2 to these two iron sources. The expression of peptide transporter 1 (PepT1) was not altered by knockout or iron treatment. Interestingly, the expression of zinc-regulated transporter (ZRT) and iron-regulated transporter (IRT)-like protein 14 (Zip14) was elevated significantly by knockout and iron treatment in wild-type cells (p < 0.05). These results indicated that iron from Fe-Gly was probably mainly transported into enterocytes via DMT1 like FeSO4; Zip14 may play a certain role in the intestinal iron transport.

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Section: Discussioncontrasting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Iron Transport from Ferrous Bisglycinate and Ferrous Sulfate in DMT1-Knockout Human Intestinal Caco-2 Cells

Chen

Ding

et al. 2019

Nutrients

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“…Cheng et al found that CTR1 and ATP7a mRNA levels declined in fish anterior intestine with increasing dietary Cu levels [37]. In the study of Liao et al, examining the different mechanisms of absorption of diverse iron sources in pig intestinal epithelial cells, PepT1 transcription expression in ferrous bisglycinate groups was significantly higher in treatments with 0.5 and 1 mM iron at 24 h, compared with ferrous sulfate [38].…”

Section: Discussionmentioning

confidence: 98%

Different Sources of Copper Effect on Intestinal Epithelial Cell: Toxicity, Oxidative Stress, and Metabolism

Wen

Lin

et al. 2019

Metabolites

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Copper (Cu) is widely used in the swine industry to improve the growth performance of pigs. However, high doses of copper will induce cell damage and toxicity. The aim of this study was to evaluate toxicity, bioavailability, and effects on metabolic processes of varying copper sources using porcine intestinal epithelial cells (IPEC-J2) as a model. The IPEC-J2 were treated with two doses (30 and 120 μM) of CuSO4, Cu Glycine (Cu-Gly), and Cu proteinate (Cu-Pro) for 10 h, respectively. Cell damage and cellular copper metabolism were measured by the changes in cell viability, copper uptake, oxidative stress biomarkers, and gene/protein expression levels. The results showed that cell viability and ratio of reduced and oxidized glutathione (GSH/GSSG) decreased significantly in all treatment groups; intracellular copper content increased significantly in all treatment groups; total superoxide dismutase (SOD) activity increased significantly in the 120 μM exposed groups; SOD1 protein expression levels were significantly upregulated in 30 μM Cu-Pro, 120 μM Cu-Gly, and 120 μM Cu-Pro treatment groups; intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) content increased significantly in 30 μM treatment groups and 120 μM CuSO4 treatment group. CTR1 and ATP7A gene expression were significantly downregulated in the 120 μM exposed groups. While upregulation of ATOX1 expression was observed in the presence of 120 μM Cu-Gly and Cu-Pro. ASCT2 gene expression was significantly upregulated after 120 μM Cu-Glycine and CuSO4 exposure, and PepT1 gene expression was significantly upregulated after Cu-Pro exposure. In addition, CTR1 protein expression level decreased after 120 μM CuSO4 and Cu-Gly exposure. PepT1 protein expression level was only upregulated after 120 μM Cu-Pro exposure. These findings indicated that extra copper supplementation can induce intestinal epithelial cell injury, and different forms of copper may have differing effects on cell metabolism.

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“…Intravenous (IV) administration of iron is the only alternative to oral administration, as intramuscular iron injections are no longer given due to the many side effects: excessive pain, abnormal skin discoloration and potential risk of developing injection site sarcoma (observed in model animals) [ 1 , 2 , 3 , 49 ]. Intravenous therapy is usually initiated when there is a severe form of IDA that requires rapid correction, forms in which a poor response to oral administration is demonstrated, or when there is difficulty in tolerability and adherence itself [ 1 , 2 , 3 , 49 , 73 ]. However, although there are numerous clinical studies on its efficacy, its application in daily management has been slow, partly due to the fear of possible adverse events, related to historical anaphylactic reactions associated with iron dextran formulations.…”

Section: Treatmentmentioning

confidence: 99%

“…However, although there are numerous clinical studies on its efficacy, its application in daily management has been slow, partly due to the fear of possible adverse events, related to historical anaphylactic reactions associated with iron dextran formulations. Studies show that rates of mild reactions are ~1 in 200 and major reactions are ~1 in 200,000 or more [ 3 , 49 , 73 ].…”

Section: Treatmentmentioning

confidence: 99%

Iron Deficiency Anemia in Celiac Disease

et al. 2021

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The iron absorption process developsmainly in the proximal duodenum. This portion of the intestine is typically destroyed in celiac disease (CD), resulting in a reduction in absorption of iron and subsequent iron deficiency anemia (IDA). In fact, the most frequent extra-intestinal manifestation (EIM) of CD is IDA, with a prevalence between 12 and 82% (in relation with the various reports) in patients with new CD diagnosis. The primary treatment of CD is the gluten-free diet (GFD), which is associated with adequate management of IDA, if present. Iron replacement treatment historically has been based on oral products containing ferrous sulphate (FS). However, the absorption of FS is limited in patients with active CD and unpredictable in patients on a GFD. Furthermore, a poor tolerability of this kind of ferrous is particularly frequent in patients with CD or with other inflammatory bowel diseases. Normalization from anemic state typically occurs after at least 6 months of GFD, but the process can take up to 2 years for iron stores to replenish.

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Ferrous bisglycinate increased iron transportation through DMT1 and PepT1 in pig intestinal epithelial cells compared with ferrous sulphate

Cited by 9 publications

References 34 publications

Iron Transport from Ferrous Bisglycinate and Ferrous Sulfate in DMT1-Knockout Human Intestinal Caco-2 Cells

Iron Transport from Ferrous Bisglycinate and Ferrous Sulfate in DMT1-Knockout Human Intestinal Caco-2 Cells

Different Sources of Copper Effect on Intestinal Epithelial Cell: Toxicity, Oxidative Stress, and Metabolism

Iron Deficiency Anemia in Celiac Disease

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