OBJECTIVENaFeEDTA was considered as a promising iron fortificant for controlling iron deficiency anemia. Soy sauce is a suitable food carrier for iron fortification and is a popular condiment in China. Iron absorption rates of NaFeEDTA and FeSO4 were observed and compared in adult female subjects.

METHODSThe stable isotope tracer method was used in Chinese females consuming a typical Chinese diet. Ten healthy young Chinese women were selected as subjects in the 15-day study. A plant-based diet was used based on the dietary pattern of adult women in the 1992 National Nutrition Survey. Six milligram of 54Fe in 54FeSO4 soy sauce and 3 mg 58Fe in Na58FeEDTA soy sauce were given to the same subjects in two days. Food samples and fecal samples were collected and analyzed.

RESULTSIron absorption rates of NaFeEDTA and FeSO4 were 10.51% +/- 2.83 and 4.73% +/- 2.15 respectively. The 58Fe (NaFeEDTA) absorption was significantly higher than that of 54Fe (FeSO4) (P < 0.01). The iron absorption rate from NaFeEDTA was 1.2 times higher than that from FeSO4 in Chinese adult women consuming a typical Chinese diet.

CONCLUSIONThe higher absorption rate of NaFeEDTA suggested that NaFeEDTA would be a better iron fortificant used in soy sauce for the controlling of iron deficiency anemia in China.

Adolescent ; Adult ; China ; Edetic Acid ; pharmacokinetics ; Female ; Ferric Compounds ; pharmacokinetics ; Ferrous Compounds ; pharmacokinetics ; Food, Fortified ; Humans ; Iron ; pharmacokinetics ; Soy Foods

OBJECTIVETo evaluate the adsorption and desorption of epirubicin (EADM) by carbon-coated iron nanocrystals (CCIN).

METHODSEADM standard curve was generated. After thorough mixture of CCIN and EADM with sonication, the mixture solution was centrifuged at high speed to obtain dissociated EADM for evaluating the adsorption capacity of CCIN. A dialyzer was used to evaluate the desorption of drug-loaded CCIN particles in different media (PBS, normal saline, or distilled water), at different temperatures, and with different quantities of loaded drug.

RESULTSThe adsorption of EADM by CCIN presented linear adsorption before saturation and saturation adsorption, with an adsorption saturation point of about 160 microg/mg. The desorption of EADM from CCIN particles was affected by such factors as the extraction media, temperature, and quantity of the loaded drug. Compared to distilled water, PBS and normal saline improved the release rate of EADM from the drug-loaded CCIN particles. Higher temperature also contributed to higher release rate of EADM. Higher release rate of EADM occurred after the CCIN particles adsorbed greater amount of EADM.

CONCLUSIONCCIN shows an EADM adsorption pattern of Langmuir isotherm adsorption. Such factors as higher temperature, PBS solution, higher speed of medium replacement, and more drug adsorbed all contribute to a higher release rate of EADM.

Adsorption ; Antibiotics, Antineoplastic ; chemistry ; pharmacokinetics ; Carbon ; chemistry ; Delayed-Action Preparations ; chemistry ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Epirubicin ; chemistry ; pharmacokinetics ; Iron ; chemistry ; Nanoparticles ; chemistry

OBJECTIVETo study the effects of ascorbic acid and citric acid on iron bioavailability using an in vitro digestion/Caco-2 cell culture model and evaluate the validity of this cell model.

METHODSThis model combined in vitro digestion technique with Fe uptake by Caco-2 cells by utilizing an inserted ring attached to a dialysis membrane to simulate the gastrointestinal environment to allow simultaneous food digestion and uptake processes. Ferritin formation in the Caco-2 cells was measured as the indicator of Fe uptake by exposing Caco-2 cells to the digests containing Fe plus ascorbic acid or citric acid.

RESULTSWhen Fe concentration in the digest was below 100 micromol/L, ferritin formation increased with the Fe concentration in the digest. The iron digest containing ascorbic acid exhibited a significant increase in ferritin formation relative to the iron digest containing citric acid. The model was more sensitive to lower iron concentrations when ascorbic acid was present in the digest, while wider range of iron concentration could be assessed by addition of citric acid.

CONCLUSIONSThe in vitro digestion/ Caco-2 cell culture model is a valuable tool for iron bioavailability assessment. Ascorbic acid has a stronger effect than citric acid in promoting iron bioavailability.

Ascorbic Acid ; pharmacology ; Biological Availability ; Caco-2 Cells ; metabolism ; Citric Acid ; pharmacology ; Ferritins ; biosynthesis ; Ferrous Compounds ; pharmacokinetics ; Humans ; Iron ; pharmacokinetics ; Models, Biological

The mechanisms by which iron is absorbed are similar to those of divalent metals, particularly manganese, lead, and cadmium. These metals, however, show different toxicokinetics in relation to menarche or menopause, although their interaction with iron is the same. This review focuses on the kinetics of these three toxic metals (manganese, lead, and cadmium) in relation to menarche, pregnancy, and menopause. The iron-manganese interaction is the major factor determining sex-specific differences in blood manganese levels throughout the whole life cycle. The effects of estrogen overshadow the association between iron deficiency and increased blood lead concentrations, explaining why women, despite having lower ferritin concentrations, have lower blood lead concentrations than men. Iron deficiency is associated with elevated cadmium levels in premenopausal women, but not in postmenopausal women or men; these findings indicate that sex-specific differences in cadmium levels at older ages are not due to iron-cadmium interactions, and that further studies are required to identify the source of these differences. In summary, the potential causes of sex-specific differences in the blood levels of manganese, lead, and cadmium differ from each other, although all these three metals are associated with iron deficiency. Therefore, other factors such as estrogen effects, or absorption rate as well as iron deficiency, should be considered when addressing environmental exposure to toxic metals and sex-specific differences in the blood levels of these metals.
Absorption ; Cadmium ; Environmental Exposure ; Estrogens ; Female ; Ferritins ; Humans ; Iron ; Kinetics ; Life Cycle Stages ; Male ; Manganese ; Menarche ; Menopause ; Metals ; Pharmacokinetics ; Pregnancy

The objective of the present study was to compare the toxicity and availability of Fe(II) and Fe(III) to Caco-2 cells. Cellular damage was studied by measuring cell proliferation and lactate dehydrogenase (LDH) release. The activities of two major antioxidative enzymes [superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and differentiation marker (alkaline phosphatase) were determined after the cells were exposed to different levels of iron salts. The cellular iron concentration was investigated to evaluate iron bioavailability. The results show that iron uptake of the cells treated with Fe(II) is significantly higher than that of the cells treated with Fe(III) (P<0.05). Fe(II) at a concentration >1.5 mmol/L was found to be more effective in reducing cellular viability than Fe(III). LDH release investigation suggests that Fe(II) can reduce stability of the cell membrane. The activities of SOD and GPx of the cells treated with Fe(II) were higher than those of the cells treated with Fe(III), although both of them increased with raising iron supply levels. The results indicate that both Fe(II) and Fe(III) could reduce the cellular antioxidase gene expression at high levels.
Antioxidants ; metabolism ; Caco-2 Cells ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Iron ; administration & dosage ; pharmacokinetics

OBJECTIVE: We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH2 and tat-CLIO. MATERIALS AND METHODS: The hNSCs (5x105 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 microgram/ml of ferumoxides, MION or CLIO-NH2, and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. RESULTS: The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15+/-0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH2, respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH2 into the hNSCs was comparable to that of tat-CLIO. CONCLUSION: For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH2 and the transfection agent PLL.
Cells, Cultured ; Contrast Media/chemical synthesis/pharmacokinetics ; Cross-Linking Reagents/chemistry ; Ferric Compounds/chemistry/*pharmacokinetics ; Ferrosoferric Oxide/chemical synthesis/pharmacokinetics ; Gene Products, tat/chemistry ; Humans ; Iron/*pharmacokinetics ; Magnetic Resonance Imaging/methods ; Nanoparticles ; Neural Tube ; Oxides/*pharmacokinetics ; Phantoms, Imaging ; Polylysine/pharmacokinetics ; Spectrophotometry, Atomic ; Staining and Labeling/*methods ; Stem Cells/cytology/*drug effects/metabolism ; Time Factors ; Transfection

AIMTo prepare magnetoliposome (MLP) containing dextran-encapsulated magnetite (Fe3O4), and to examine its physicochemical properties and its in vivo behavior on ICR mice.

METHODSReverse phase evaporation method was used to formulate MLP and the Fe2+ concentration was measured by o-phenanthroline method. Then the basic properties of MLP and in vivo distribution were studied with the aid of 3H isotope as biomarker.

RESULTSThe mean diameter of MLP was 602.5 nm and the final concentration of encapsulated Fe3O4 was 88.1 mg x L(-1). Under natural conditions most of the MLP was taken up by spleen after the administration via tail vain, but its uptake was reduced under the magnetic field. There was a great difference in vivo distribution between the left and right lobes of the liver and the left and right kidneys in magnetic fields.

CONCLUSIONReverse phase evaporation method was utilized to prepare magnetoliposomes. The formulation was stable and encapsulated high amount of magnetite. The delivery system could be oriented to certain tissues under magnetic field and satisfying magnetic responsiveness was observed.

Animals ; Dextrans ; administration & dosage ; pharmacokinetics ; Drug Delivery Systems ; Female ; Ferrosoferric Oxide ; Iron ; administration & dosage ; pharmacokinetics ; Kidney ; metabolism ; Liposomes ; Liver ; metabolism ; Magnetics ; Male ; Mice ; Mice, Inbred ICR ; Nanotechnology ; Oxides ; administration & dosage ; pharmacokinetics ; Particle Size ; Spleen ; metabolism

OBJECTIVETo establish a method for detecting plasma concentration of corn polysaccharide iron complex (CPIC) and investigate its absorption, distribution and elimination in rats.

METHODSUsing radioactivity isotope tracing method, we detected the radioactivity of (59)Fe-CPIC in the plasma of rats at different time points by gavages of 3 doses (28.0, 14.0, and 7.0 mg/kg) (59)Fe-CPIC in SD rats. The pharmacokinetic parameters was obtained using DAS 2.0 program for analysis of tissue distribution and elimination of (59)Fe-CPIC.

RESULTSThe standard curve was linear within the range of 0.14-141 µg/ml (r=0.9999, n=5). The average recovery was 95% with a relative standard deviation no more than 15%. The pharmacokinetic parameters at 3 doses obtained, namely t1/2 and AUC (0-), were 214∓104, 231∓110, and 181∓81 min, and 1986.3∓513.3, 737.0∓467.0, and 315.1∓226.1 mg·min-1·L(-)1, respectively. (59)Fe-CPIC were detected in all the 13 tissues types examined and high radioactivity intensity was found in the gastrointestinal tract, hematogenic organs and other organs rich in blood. (59)Fe-CPIC was eliminated after intragastric administration primarily via the feces in rats.

CONCLUSIONThe method we established is easy and specific, and the pharmacokinetic parameters of (59)Fe-CPIC fit the two- compartment open model.

Administration, Oral ; Animals ; Area Under Curve ; Coordination Complexes ; administration & dosage ; pharmacokinetics ; urine ; Feces ; chemistry ; Female ; Intestinal Absorption ; Iron ; administration & dosage ; pharmacokinetics ; urine ; Iron Radioisotopes ; Male ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacokinetics ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution ; Zea mays ; chemistry

Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fethan normal cells, there are a large number of transferrin receptors on the tumor cell membrane. DHA can break the peroxide bridge in the presence of Fe, and the free radicals generated can play its lethal effect on tumor cells. In addition, DHA can promote endocytosis of transferrin receptor, and thus prevent cancer cells from taking Fefrom microenvironment. This article reviews the anti-tumor molecular mechanism of DHA, including accelerating oxidative damage, inducing apoptosis, inhibiting the growth, proliferation and invasion of tumor cells, reversing tumor multidrug resistance.
Antigens, CD ; drug effects ; metabolism ; Antineoplastic Agents ; pharmacokinetics ; pharmacology ; Apoptosis ; drug effects ; Artemisinins ; metabolism ; pharmacokinetics ; pharmacology ; Endocytosis ; drug effects ; Free Radicals ; chemical synthesis ; pharmacology ; Humans ; Iron ; metabolism ; Neoplasms ; drug therapy ; physiopathology ; Oxidative Stress ; drug effects ; Receptors, Transferrin ; drug effects ; metabolism

OBJECTIVETo compare iron bioavailability (Fe BV) from ten selected kinds of Chinese wheat flours in order to provide scientific basis for further human trials and enable plant breeding programs to screen biofortified wheat cultivars.

METHODSAn in vitro digestion/Caco-2 cell model was used to assess Fe BV of ten flour samples from six leading Chinese wheat cultivars and the stability of Fe BV in one cultivar was studied across three growing environments.

RESULTSSignificant differences were observed in both Fe BV and Fe bioavailability per gram of food (Fe BVPG) among cultivars (P<0.01) grown at the same location with the same flour extraction rate. Zhongyou 9507 and Jingdong 8 had Fe BV 37%-54% and Fe BVPG 103%-154% higher than the reference control. In the Anyang environment, Zhongyou 9507 had a higher wheat flour-Fe level and Fe BVPG. Differences in Fe BV were detected in cultivars with different flour extraction rates.

CONCLUSIONZhongyou 9507 and Jingdong 8 were identified as the most promising cultivars for further evaluation of efficacy by using human subjects. The growing environments had no effect on Fe BV, but did have a significant effect on Fe BVPG. Fe bioavailabilities in low-extraction (40%) flours were higher than those in high-extraction (78%) flours.

Biological Availability ; Caco-2 Cells ; China ; Ferritins ; chemistry ; Flour ; analysis ; Genetic Variation ; Humans ; Iron ; chemistry ; pharmacokinetics ; Phosphorus ; chemistry ; Phytic Acid ; chemistry ; Triticum ; chemistry ; genetics