Caseinophosphopeptide-Bound Iron: Protective Effect against Gut Peroxidation

Abstract

Background: Peptides derived from cow’s milk proteins have in vitro protective effects on iron-induced peroxidation that could be used to prevent the side effects of iron fortification. The aim of the study was to confirm these properties in an in vivo model of gut peroxidation. Methods: Iron bound to the 1–25 phosphopeptide of β-casein [Fe-β-CPP(1–25)] was compared to an encapsulated ferric pyrophosphate (Fe-P) in the Caco-2 model. Ferrous sulfate (FeSO₄) was used as control (100 µmol/l iron, n = 6 per group). The concentration of malondialdehyde (MDA), a stable byproduct of lipid peroxidation, was used as the marker of peroxidation. Results: The lowest MDA levels were observed in cells grown with Fe-β-CPP(1–25) and the highest with Fe-P. Iron absorption of Fe-β-CPP(1–25) was higher than in the 2 other forms, due to its high cellular uptake and high basolateral transfer, while iron absorption of Fe-P showed high uptake and high cell retention. Conclusions: The enhancing effect of β-CPP(1–25) on iron absorption was associated with a protective effect against enterocyte peroxidation, perhaps due to its low storage by enterocytes. These observations support a role for specific milk components in food fortification to prevent iron deficiency.

Caseinophosphopeptides exert partial and site-specific cytoprotection against H2O2-induced oxidative stress in Caco-2 cells

“…According to this, a decrease in MDA production due to the addition of certain PPP fractions prior to treatment with H 2 O 2 in Caco-2 cells has been attributed to the presence of phosphorus in these fractions (Katayama et al, 2006). This protection against lipid peroxidation in H 2 O 2 -induced oxidative stress in Caco-2 cells by a pool of CPPs (to our knowledge reported here for the first time) is in agreement with the results reported by Kibangou et al (2008) using a specific CPP (b-CN(1-25)) bound to iron in Caco-2 cells without induced stress. These authors showed that the complex between b-CN(1-25) and iron decreased or maintained the MDA levels versus iron sulphate or the control, respectively, suggesting a protective effect of this complex against iron-induced peroxidation.…”

“…In this sense, Katayama, Xu, Fan, and Mine (2006) and Katayama, Ishikawa, Fan, and Mine (2007) have reported that oligophosphopeptides derived from hen egg yolk exert an antioxidant effect against H 2 O 2 , diminishing lipid peroxidation and interleukin-8 secretion, and causing the up-regulation of glutathione (GSH) induced biosynthesis, accompanied by an increase in glutathione reductase (GSH-Rd) and c-glutamylcysteine synthetase activity (c-GCS), as well as the induction of glutathione-S-transferase (GST) and catalase (CAT). To our knowledge, the antioxidant and cytomodulatory activity of CPPs has been previously reported in Caco-2 cells by Kibangou et al (2008); Laparra, Alegría, Barberá, and Farré (2008). The former authors studied the effect of a specific CPP (b-CN(1-25)) against lipid peroxidation, while the latter authors evaluated the effect of a pool of CPPs at 1.4 mg/ml (obtained by simulated gastrointestinal digestion) in comparison to fruit beverages with/without milk, against H 2 O 2 -induced oxidative stress, and reported a potential cytoprotective effect by preserving cell cycle distribution and GSH-Rd induction.…”

The chelating peptide (GPAGPHGPPG) derived from Alaska pollock skin enhances calcium, zinc and iron transport in Caco‐2 cells

“…Similarly, Kibangou et al . () discovered that the transport of iron bound to β‐CN(1–25) was higher than in the case of iron sulphate or iron pyrophosphate. Besides, they also reported a decrease in iron retention.…”

“…Wortley et al (2005) reported that in Caco-2 cell model, the addition of milk increased iron availability from ferric sulphate fortified cereal and indicated that the milk proteins perhaps prevent some of the binding of iron to iron absorption inhibitors such as phytates and phenolics. Similarly, Kibangou et al (2008) discovered that the transport of iron bound to b-CN(1-25) was higher than in the case of iron sulphate or iron pyrophosphate. Besides, they also reported a decrease in iron retention.…”

“…Mineral‐chelating peptides, which possess the ability to bind with metal ions or to enhance mineral absorption in the gastrointestinal tract, have been regarded as effective functional ingredients to enhance dietary mineral bioavailability and widely employed in food products such as oatmeal, biscuits and milk powder (Guo et al ., ). Casein phosphopeptides (CPPs), for instance, derived from milk protein have been confirmed to chelate with calcium, zinc and iron and promote the mineral absorption both in vitro and in vivo (Hansen et al ., ; Kibangou et al ., ; García‐Nebot et al ., , , ). Besides, soy bean, oat bran, wheat germ, oyster and whey protein are all confirmed as food protein sources of chelating peptide (Lv et al ., ; Baakdah & Tsopmo, ; Cruz‐Huerta et al ., ; Udechukwu et al ., ).…”