Intrauterine Vitamin B2 Uptake of Preterm and Full-Term Infants

Abstract

Intrauterine uptake of vitamin B, in preterm and full-term infants was examined. Factors of influence on vitamin supply were considered. Forty-four women and their infants were included in the study. Fetal vitamin uptake was calculated as arteriovenous concentration gradient in cord plasma times umbilical plasma flow. Concentration of vitamin B, (free riboflavin and flavocoenzymes) was determined by high performance liquid chromatography of placental tissue and blood plasma (maternal vein, umbilical artery, umbilical vein). Flavocoenzymes were analyzed as flavin mononucleotide after acid hydrolysis of flavin adenine dinucleotide. Umbilical plasma flow was measured using pulsed Doppler sonography. Both free riboflavin and flavocoenzymes were transferred from the maternal plasma to the umbilical vein, but only free riboflavin was accumulated (-1:4 for preterm and full-term infants, respectively). Flavocoenzyme concentration was higher in the umbilical vein than in the umbilical artery (p < 0.05). This indicated a median uptake of flavocoenzymes of 1.5 nmol/miwkg in preterm infants and 0.4 nmoll miwkg in full-term infants (preterm versus full-term, p < 0.01). Arteriovenous concentration differences in umbilical blood have been reported for a variety of nutrients, e.g. amino acids or glucose (1, 2). In general, concentrations of these nutrients have been found to be more elevated in plasma from the umbilical vein than the umbilical artery. Such differences suggest a fetal uptake of nutrients (Fig. 1); however, they do not allow any quantitative assessment. To be able to quantify fetal uptake, it is not only necessary to determine arteriovenous gradients, but also plasma flow in cord vessels (4). (8,9). In such instances a reduced transplacental transfer is expected to occur (10). The placenta's role is threefold: to sequester free riboflavin and flavocoenzymes, to hydrolyze the majority of the flavocoenzymes to yield free riboflavin, and to release both free riboflavin and its coenzyme forms into fetal circulation (5, 11).The build-up of a riboflavin concentration gradient was also

HepG2 cells develop signs of riboflavin deficiency within 4 days of culture in riboflavin-deficient medium

“…Afflicted individuals are likely to develop signs of riboflavin deficiency as described here. Consistent with this notion, the riboflavin-deficient medium used in the present study contained a concentration of riboflavin (3.1 nmol/L) similar to that observed in plasma from moderately deficient pregnant women [11]. However, we shall point out that liver cells are supplied with water-soluble nutrients through the portal vein in vivo, and that riboflavin concentrations are greater in portal blood compared with peripheral blood [13].…”

“…Evidence has been provided that plasma concentrations of riboflavin may decrease in pregnancy [11] and in response to treatment with antimalarial drugs [1]. Moreover, riboflavin deficiency has been observed in preterm newborns treated with phototherapy [29] and in patients with cystic fibrosis [30].…”

“…Riboflavin concentrations in media were chosen based on the following lines of reasoning. First, previous studies provided evidence that HepG2 cells develop severe riboflavin deficiency if cultured in medium containing 3.1 nmol/L riboflavin for eight days [5]; this concentration represents the level of riboflavin observed in plasma from moderately deficient pregnant women [11]. Second, previous studies provided evidence that a concentration of 532 nmol/L riboflavin in culture medium is sufficient to prevent riboflavin deficiency in HepG2 cells [5]; this concentration represents the level of riboflavin observed in plasma from individuals taking riboflavin supplements [12] and in normal portal vein blood [5,13].…”

Riboflavin deficiency causes protein and DNA damage in HepG2 cells, triggering arrest in G1 phase of the cell cycle

“…Riboflavin concentrations in media were chosen based on the following. First, previous studies provided evidence that HepG2 cells develop signs of riboflavin deficiency if cultured in medium containing 3.1 nmol/L riboflavin [5]; this concentration represents the level of riboflavin observed in plasma from moderately deficient pregnant women [15]. Second, previous studies provided evidence that a concentration of 300 nmol/L riboflavin in culture medium prevents signs of riboflavin deficiency in HepG2 cells [5]; this concentration represents the level of riboflavin observed in plasma from individuals taking riboflavin supplements [16] and in portal vein blood [5,17].…”

Dynamin 2 Regulates Riboflavin Endocytosis in Human Placental Trophoblasts

“…It is noteworthy that the successful design of drug-targeting strategies and therapeutic applications can only occur upon thorough molecular characterization of ligand-associated RME systems. The molecular sensors regulating riboflavin (vitamin B 2 ) homeostasis is a relatively unexplored pathway that has gained recent attention for its proposed importance in fetal development and breast and liver cancer physiology (Zempleni et al, 1995;Rao et al, 1999Rao et al, , 2006. Vitamin B 2 is an essential nutrient required by oxidation-reduction pathways critical in normal cellular growth, function, and maintenance.…”