In HT1080 cells, 5 mM of iron(III) ammonium citrate (ferric ammonium citrate; 1, 5, 10, 15 mM; 24 hours) causes cell death. AML12 cells retain over 80% of their viability and exhibit a high level of resistance to iron(III) ammonium citrate. Potential transporter activity allows the entry of iron(III) citrate into cells. [1] Chlorella FSP-E (CV), 12 mg/L and 18 mg/L, has increased biomass in the iron (III) citrate (6, 12, 18 mg/L) medium in BG-11[2].

Absorption, Distribution and Excretion
This study investigated the absorption and endogenous excretion of iron in the human body by monitoring the excretion of stable iron isotope (58Fe) in feces. Twelve healthy volunteers were divided into two groups. The first group received the equivalent of 6 mg of 58Fe-labeled ferric ammonium citrate (III) (58FeAC) as a control, while the second group received a combination of 500 mg of vitamin C and 58FeAC. A novel formula was used to calculate the 58Fe absorption rate reflecting the iron pool in intestinal cells, and this ratio was compared with the results calculated using the Janghorbani formula, a commonly used method. The results showed that, calculated using the Janghorbani formula, the 58Fe absorption rate in the second group was significantly higher than that in the first group (34.4 ± 6.1% vs. 15.0 ± 5.5%, mean ± standard deviation). Our proposed new formula also yielded a similar absorption rate (34.1 ± 6.0% vs. 14.8 ± 5.5%). Our results confirm previous findings that vitamin C supplementation can promote iron utilization. The iron absorption rates calculated by both formulas were consistent, indicating that the excretion of endogenous iron from the gut (caused by exfoliated cells) does not mask iron absorption. We evaluated the absorption of a commercially available small-particle reduced iron in 10 healthy subjects. For each subject, we used the hemoglobin incorporation method to determine the true absorption rate of iron from 60 mg of ferrous sulfate or ferric ammonium citrate. This study also included an iron tolerance test (ITT) for both compounds and reduced iron. This test involved measuring the area under the curve of plasma iron concentration increases over a sustained 6-hour period at specific time points, or measuring peak plasma iron levels, corrected for by the rate of iron disappearance. The rate of iron disappearance was obtained by measuring plasma iron concentrations at specific time points over a sustained 4-hour period following a slow intravenous injection of 0.4 mg ferric citrate. The absorption of 60 mg of reduced iron was measured using only the ITT. The absorption of a reference dose of ferric ascorbate was measured for each subject. The absorption rates of ferric ammonium citrate and reduced iron are expressed as a percentage of dose and a percentage of ferrous sulfate absorption. The mean geometric "true absorption rates" are: 39.0% at the reference dose, 10.4% for ferrous sulfate, and 2.4% for ferric ammonium citrate. The latter is 23% of the ferrous sulfate absorption rate. Measured by the ITT method, the mean geometric absorption rates of ferrous sulfate, ferric ammonium citrate, and reduced iron are 7.9%, 3.7%, and 3.2%, respectively, equivalent to 47% and 41% of the ferrous sulfate absorption rate. Based on the relationship between the ITT results of reduced iron and the ITT results of ferric ammonium citrate relative to ferrous sulfate and the true absorption rates, we believe that the true absorption rate of the commercially available reduced iron tested is approximately 20% of that of ferrous sulfate.

[1]. Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors. Biochem Biophys Res Commun. 2018 Sep 3;503(1):297-303.

[2]. Towards protein production and application by using Chlorella species as circular economy. Bioresour Technol. 2019 Oct;289:121625.

Ferrous ammonium citrate is a yellowish-brown to red solid with a slight ammonia odor and is readily soluble in water. Its main hazard lies in its environmental impact. Immediate measures should be taken to limit its environmental spread. Ferrous ammonium citrate is used in pharmaceuticals, drafting, and as a feed additive.
See also: Ferrous ammonium citrate (note moved to).

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Mechanism of Action
...After incubation with 0.36 mmol/L ferrous ammonium citrate for 24 hours, the activity of nicotinamide adenine dinucleotide (NADH)-cytochrome c oxidoreductase (complex I+III) decreased to 35.3% ± 11.2% of the untreated control group; the activity of succinate-cytochrome c oxidoreductase (complex II+III) decreased to 57.4% ± 3.1% of the untreated control group; and the activity of succinate dehydrogenase decreased to 63.5% ± 12.6% (p < 0.001 in all cases). Other mitochondrial enzyme activities showed smaller reductions, including NADH-ferricyanide reductase, succinate ubiquinone oxidoreductase (complex II), cytochrome c oxidase (complex IV), and ubiquitin-cytochrome c oxidoreductase (complex III), with reductions ranging from 71.5% ± 15.8% to 91.5% ± 14.6% compared to the control group. In vitro iron chelation therapy completely restored enzyme activity, clearly demonstrating that the observed reductions in respiratory enzyme activity were a specific effect of iron toxicity. Sequential treatment with iron and doxorubicin resulted in greater reductions in the activities of complexes I+III and II+III than either drug alone, but these reductions were only partially corrected by DF treatment. Changes in intracellular adenosine triphosphate (ATP) measurements closely mirrored changes in respiratory complex activity.

C6H11FENO7

264.9990

261.965

1185-57-5

14457

Light brown to brown solid powder

1.8 g/cm3 (20ºC)

197ºC

2

8

2

15

211

0

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~33.33 mg/mL
DMSO :< 1 mg/mL

Solubility in Formulation 1: 50 mg/mL (Infinity mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)