Bovine plasma hydrolysates’ iron chelating capacity and its potentiating effect on ferritin synthesis in Caco-2 cells

Bovine plasma hydrolysates with a degree of hydrolysis of 19.1% have an iron chelating capacity of 38.5 ± 0.4% and increase the synthesis of ferritin in Caco-2 cells five-fold compared to the control.

Hereditary hyperferritinaemia-cataract syndrome (HHCS) – an underestimated condition: ferritin light chain variant spectrum in German families

Background In hereditary hyperferritinaemia-cataract syndrome (HHCS), single nucleic acid alterations in the ferritin light chain (L-ferritin) iron response element (IRE) constitutively derepress ferritin synthesis, resulting in hyperferritinaemia, L-ferritin deposits in the lens of the eye and early bilateral cataract onset. Methods In this study, six German families with putative HHCS were analysed. Clinical diagnosis of HHCS was based on medical history, evaluation of ferritin serum levels, transferrin saturation and clinical ophthalmological examination. Diagnosis was confirmed by polymerase chain reaction (PCR)-based DNA sequencing of the L-ferritin IRE. Results Genetic analysis of the L-ferritin IRE revealed relevant single nucleic acid alterations in each of the affected families. Variants c.-168G > A, c.-168G > U and c.-167C > U were located in the C-bulge region; and variants c.-161C > U and c.-157G > A were located in the hexanucleotide loop of the L-ferritin IRE. Conclusions Family history of hyperferritinaemia and juvenile cataracts are strong indicators of HHCS. Genetic analysis of the L-ferritin IRE is a straightforward procedure to confirm the diagnosis. Accurate diagnosis of hyperferritinaemia can avoid unnecessary treatment by venesection, and focus attention on early cataract detection in offspring at risk.

Sucrosomial Iron®: A New Highly Bioavaible Oral Iron Supplement

Introduction: Iron deficiency is one of the most widespread nutritional deficiencies. Globally two billion people are suffering from iron- deficiency anemia (Hermida et al., 2010). Oral therapy for iron deficiency is mainly based on immediate release formulations of ferrous iron. However, modified formulations have been marketed to reduce gastrointestinal side effects and to prevent iron instability in the gastrointestinal tract. Overcoming biological barriers, including the gastrointestinal epithelial barriers, is a great challenge for pharmaceutical research and thus there is a need for new absorption enhancers with more favorable profile. Sucrose esters are widely used in the food industry, and there are reports on their potential use in pharmaceutical formulations as excipients (Szuts A et al., 2008). In vitro methods using cell cultures have been proposed to assess iron bioavailability as an alternative to in vivo methods. Caco-2 cells have shown numerous morphological and biochemical characteristics of enterocytes and have been successfully used to study iron absorption (Garcia et al., 1996; Jovani et al., 2001). Caco-2 monolayers formed a good barrier as reflected by high transepithelial resistance and positive immunostaining for junctional proteins. Sucrose esters in nontoxic concentrations significantly reduced resistance and impedance, and increased permeability of some components in Caco-2 monolayers. Recent data indicate that sucrose esters can enhance drug permeability through both the transcellular and paracellular routes (Kiss et al., 2014). Aim: The strong correlation between the published human absorption data and the iron uptake by Caco-2 cells makes them an ideal in vitro model to study iron bioavailability (Au and Reddy, 2000). For this, in the present study, we compared the bioavailability of innovative Oral Iron formulation based on Sucrosomial Iron¨ (Sideral¨) with three different Iron formulations (Figure 1). Materials and Methods: Sucrosomial Iron, preparation of ferric pyrophosphate convered by a phospholipids plus sucrose esters of fatty acids matrix; Lipofer¨, a water-dispersible micronised iron; Sunactive¨ ferric pyrophosphate, lecithin and emulsifiers. Results: The data showed that Sucrosomial Iron¨ (Sideral¨), is significantly more bioavaible than microencapsulated Ferric pyrophosphate ingredients, Lipofer¨ and Sunactive¨ and Ferrous Sulfate in Caco-2 cell model (Figure 1). Bibliography Au, A. P., Reddy, M. B. (2000). Caco-2 cells can be used to assess human iron bioavailability from a semipurified meal. J Nutr 130:1329-1334. Garcia et al. (1996). The Caco-2 cell culture system can be used as a model to study food iron availability. J Nutr 126:251-258. Hermida et al., Preparation and characterization of iron-containing liposomes: their effect on soluble iron uptake by Caco-2 cells Journal of Liposome Research, 2010, 1-10, Jovani et al. (2001) Calcium, iron, and zinc uptake from digests of infant formulas by Caco-2 cells. J Agric Food Chem 49:3480-3485. Kiss et al., (2014) Sucrose esters increase drug penetration, but do not inhibit p-glycoprotein in caco-2 intestinal epithelial cells J Pharm Sci. Oct;103(10):3107-19. Szuts A et al. (2008) Study of the effects of drugs on the structures of sucrose esters and the effects of solid-state interactions on drug release J Pharm Biomed Anal. 48: Figure 1. the graph shows the Ferritin levels of Caco-2 cells after iron formulations treatment. Sucrosomial Iron treated cells display significant increase of Ferritin synthesis compared to Lipofer and SunActive treated cells. Figure 1. the graph shows the Ferritin levels of Caco-2 cells after iron formulations treatment. Sucrosomial Iron treated cells display significant increase of Ferritin synthesis compared to Lipofer and SunActive treated cells. Disclosures Tarantino: Pharmanutra s.p.a.: Employment. Brilli:Pharmanutra s.p.a.: Employment.

Hereditary Hyperferritinemia-cataract Syndrome

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare autosomal dominant disorder associated with high plasma ferritin concentration without iron overload and early-onset bilateral cataract. The deregulation of ferritin production in HHCS is caused by mutations in the iron-responsive elements (IREs) of the ferritin L-subunit gene (FTLgene) – interfering with the high-affinity interaction between IREs and iron regulatory proteins (IRPs), disturbing the negative regulatory control of ferritin synthesis and resulting in excessive production of L-ferritin. We report a 44-year-old woman initially suspected of having hereditary haemochromatosis and later together with family members diagnosed with HHCS. Genetic analysis showed heterozygosity for a G32T point mutation (Paris 2 mutation) in the IRE located in the 5' untranslated region (UTR) of theFTLgene. The differential diagnosis of hereditary haemochromatosis and HHCS together with the rarity and the versatile phenotype in HHCS obscures the diagnostic process, which emphasises the importance of the correct diagnosis of HHCS in order to prevent unnecessary phlebotomy.