Humans must obtain vitamin B9 (folate) from plant-based diet. The sources as well as the effect of food processing are discussed in detail. Industrial production, fortification and biofortification, kinetics, and physiological role in humans are described. As folate deficiency leads to several pathological states, current opinions toward prevention through fortification are discussed. Claimed risks of increased folate intake are mentioned as well as analytical ways for measurement of folate.
Human serum albumin (HSA) is the most abundant plasma protein in circulation. The three most important drug-binding sites on HSA are Sudlow’s Site I (subdomain IIA), Sudlow’s Site II (subdomain IIIA), and Heme site (subdomain IB). Heme site and Site I are allosterically coupled; therefore, their ligands may be able to allosterically modulate the binding affinity of each other. In this study, the effects of four Heme site ligands (bilirubin, biliverdin, hemin, and methyl orange) on the interaction of the Site I ligand warfarin with HSA were tested, employing fluorescence spectroscopic, ultrafiltration, and ultracentrifugation studies. Our major results/conclusions are the following. (1) Quenching studies indicated no relevant interaction, while the other fluorescent model used suggested that each Heme site ligand strongly decreases the albumin binding of warfarin. (2) Ultrafiltration and ultracentrifugation studies demonstrated the complex modulation of warfarin–HSA interaction by the different Heme site markers; for example, bilirubin strongly decreased while methyl orange considerably increased the bound fraction of warfarin. (3) Fluorescence spectroscopic studies showed misleading results in these diligand–albumin interactions. (4) Different Heme site ligands can increase or decrease the albumin binding of warfarin and the outcome can even be concentration dependent (e.g., biliverdin and hemin).
Data on alkaloid interactions with the physiologically important transition metals, iron and copper, are mostly lacking in the literature. However, these interactions can have important consequences in the treatment of both Alzheimer’s disease and cancer. As isoquinoline alkaloids include galanthamine, an approved drug for Alzheimer’s disease, as well as some potentially useful compounds with cytostatic potential, 28 members from this category of alkaloids were selected for a complex screening of interactions with iron and copper at four pathophysiologically relevant pH and in non-buffered conditions (dimethyl sulfoxide) by spectrophotometric methods in vitro. With the exception of the salts, all the alkaloids were able to chelate ferrous and ferric ions in non-buffered conditions, but only five of them (galanthine, glaucine, corydine, corydaline and tetrahydropalmatine) evoked some significant chelation at pH 7.5 and only the first two were also active at pH 6.8. By contrast, none of the tested alkaloids chelated cuprous or cupric ions. All the alkaloids, with the exception of the protopines, significantly reduced the ferric and cupric ions, with stronger effects on the latter. These effects were mostly dependent on the number of free aromatic hydroxyls, but not other hydroxyl groups. The most potent reductant was boldine. As most of the alkaloids chelated and reduced the ferric ions, additional experimental studies are needed to elucidate the biological relevance of these results, as chelation is expected to block reactive oxygen species formation, while reduction could have the opposite effect.
Bisphenols are frequently used in the plastic industry. However, there is a need for addressing their safety in in vivo studies based on the observed negative impact of bisphenol A. Bisphenol AP (BPAP) is frequently found in the environment, human food, and biological fluids, but its cardiovascular effects have not yet been tested. For this reason, we administered BPAP in a daily single dose of 2.5 mg.kg-1via oral gavage to eight male Wistar Han rats for a period of 4 weeks. Eight control rats received the solvent, sesame oil. Parent BPAP was detectable in plasma only in 3 animals by a validated LC-MS/MS method, whereas its glucuronide was found in all animals (48.4 ± 25.4 nM). Arterial blood pressure did not change during or at the end of the treatment. Some disturbances in cardiac rhythm were observed (e.g., increased heart rate, prolonged P wave and QTpeak interval, p < 0.05), but there was no increase in serum cardiac troponin T. Vessels isolated from BPAP-treated animals showed impaired vasodilatory response compared to control animals (p < 0.05). BPAP impacted coagulation and caused hemolysis only in hundreds of µM concentrations. These results demonstrate the potential of BPAP to affect cardiac rhythm and impair vessel homeostasis after subacute exposure.
Bisphenols, frequently used in the plastics industry, have been recognized as environmental pollutants. Bans on bisphenol A use led to the replacement by alternatives. There are, however, almost no data on their biological effects in humans. This study has focused on the potential negative impact of four alternatives to bisphenol A on haemostasis and erythrocytes. Acute toxicity was assessed using rat and human erythrocytes, followed by a lactate dehydrogenase assay. The impact on platelet aggregation was initially screened in whole human blood, followed by a thorough investigation of the mechanism of action at different levels. Haemocoagulation was also assessed. The erythrocyte toxicity of all tested compounds was relatively low, with TC50s above 500 μM in all cases. None of the compounds augmented platelet aggregation, but DD-70 was a potent antiplatelet compound with an IC50 of 5.0 ± 2.7 µM in arachidonic acid-triggered platelet aggregation. DD-70 also blocked other aggregation pathways, and its mechanism was primarily based on the inhibition of cyclooxygenase 1. Only high concentrations of the tested bisphenol A alternatives (≥100 µM) influenced blood coagulation. Based on these results, DD-70 may affect platelet aggregation and have clinical consequences due to its low IC50, however, this hypothesis requires a human exposure study to be confirmed. ENVIRONMENTAL IMPLICATIONS: Due to the enormous amounts of bisphenols used in the chemical industry, they represent important environmental pollutants. Their accumulation both in the environment and the human body has a negative influence on nature and the health of the population. While the most infamous representative, bisphenol A, is being banned in developed countries, the lack of knowledge on the biological effects of its substitutes poses a grave danger. Our study shows that one of these alternatives may, in fact, negatively impact the haemostasis of both humans and animals, which may have negative implications, in particular for occupational healthcare and food production.