High-level production of animal-free recombinant transferrin from Saccharomyces cerevisiae.

Background: Animal-free recombinant proteins provide a safe and effective alternative to tissue or serum-derived products for both therapeutic and biomanufacturing applications. While recombinant insulin and albumin already exist to replace their human counterparts in cell culture media, until recently there has been no equivalent for serum transferrin.

Results: The first microbial system for the high-level secretion of a recombinant transferrin (rTf) has been developed from Saccharomyces cerevisiae strains originally engineered for the commercial production of recombinant human albumin (Novozymes' Recombumin® USP-NF) and albumin fusion proteins (Novozymes' albufuse®).

In vitro study on the effects of iron sucrose, ferric gluconate and iron dextran on redox-active iron and oxidative stress.

Concerns exist that administration of intravenous (i.v.) iron preparations is associated with oxidative stress.

Iron availability and complex stability of iron hydroxyethyl starch and iron dextran a comparative in vitro study with liver cells and macrophages.

Background: Intravenous iron (IVI) therapy is required in patients with end-stage renal disease (ESRD) under chronic haemodialysis (HD). In this in vitro study we investigated the availability and stability of iron hydroxyethyl starch (iron-Hes) compounds in THP-1 cells (macrophage phenotype) and liver cells (HepG2 cells) and compared it with the well-known iron dextran.

Methods: The uptake and release of these iron formulations by THP-1 cells (macrophage phenotype) and HepG2 cells were investigated with atomic absorption spectrometry (AAS).

Differential response of iron metabolism to oxidative stress generated by antimycin A and nitrofurantoin.

The close interrelationship of oxidative stress and iron is evident by the influence of intracellular reactive oxygen species on iron metabolism. Oxygen radicals can lead to release of iron from iron-sulfur proteins and ferritin, and can damage iron-containing enzymes such as mitochondrial aconitase. Treatment of HepG2 human hepatoma cells with antimycin A has two effects relating to iron depending on the concentrations of antimycin A: increase of the labile iron pool and stimulation of non-transferrin-bound iron uptake.

Intravenous iron preparations and ascorbic acid: effects on chelatable and bioavailable iron.

Background: There is growing interest to use ascorbic acid as adjuvant therapy for patients with recombinant human erythropoietin-hyporesponsiveness (rHuEpo). Several clinical studies showed the beneficial effect of ascorbic acid treatment on hematologic parameters in rHuEpo-treated hemodialysis patients with elevated or even normal iron stores. However, whether ascorbic acid directly affects stability and cellular metabolism of intravenous iron preparations (IVI) is not well understood.