Not a therapeutic target; it is a radiocontrast agent used for X-ray/CT imaging to increase the visibility of internal structures. [1]

For two to twenty-four hours, HK-2 cells were treated to either a vehicle or 0–30 mg I/mL sodium diatrizoate (sodium diatrizoate salt). According to the MTT and trypan blue exclusion experiments, cell viability and mitochondrial content drop after two and twenty-four hours, respectively [2].

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This study primarily focuses on the formulation and physical characterization of diatrizoate sodium nanoparticle agglomerates, not on its pharmacological activity. The nanoparticles and agglomerates were characterized for particle size, zeta potential, aerodynamic properties, and dissolution rate. [1]
In vitro dissolution studies in phosphate-buffered saline (PBS, pH 7.4) showed that diatrizoate sodium released from nanoparticle agglomerates reached 100% after 2 hours, which was slower than from pure nanoparticles (100% in 90 minutes) but faster than from the bulk drug powder as received (100% in 4 hours). The release kinetics for all forms followed the Higuchi model. [1]

Sodium diatrizoate is an iodinated radiographic contrast agent. After insufflation of sodium diatrizoate nanoparticle aggregates, histological analysis of rat lung tissue revealed no acute toxicity or inflammation. Sodium diatrizoate nanoparticle agglomerates present a promising alternative for safe and efficient lung visualization [1].

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Superoxide dismutase (SOD) activity was measured using a spectrophotometric kit. Total SOD, MnSOD (mitochondrial), and Cu/ZnSOD (cytosolic) activities were assessed. To measure Cu/ZnSOD activity specifically, samples were pre-incubated with sodium diethyldithiocarbamate to inhibit Cu/ZnSOD, and MnSOD activity was then measured. The difference between total and MnSOD activity represented Cu/ZnSOD activity. [2]
Calpain activity was measured using a commercial activity assay kit according to the manufacturer's instructions. The assay was performed in a 96-well plate format. [2]

Mitochondrial and Cell Viability: HK-2 cells were seeded in 96-well plates and treated with DA (0–30 mg I/mL) for 2, 8, or 24 hours. Mitochondrial viability was assessed via MTT assay, where the yellow tetrazolium dye MTT is reduced to purple formazan by mitochondrial dehydrogenases. Cell viability and membrane integrity were assessed via trypan blue exclusion assay, where live cells exclude the dye, and dead cells take it up. Cell counting was performed using an automated cell counter. [2]
Seahorse XF Metabolic Assays: HK-2 cells were cultured in specialized microplates. For mitochondrial stress tests, cells were treated with DA, then sequentially injected with oligomycin (ATP synthase inhibitor), FCCP (uncoupler), and rotenone/antimycin A (Complex I/III inhibitors) while measuring Oxygen Consumption Rate (OCR). For glycolysis stress tests, cells were starved, then sequentially injected with glucose, oligomycin, and 2-deoxyglucose (hexokinase inhibitor) while measuring Extracellular Acidification Rate (ECAR). Real-time ATP rate and mitochondrial fuel flex tests were also performed following standard Seahorse protocols with appropriate inhibitors (UK5099 for pyruvate carrier, BPTES for glutaminase, etomoxir for fatty acid oxidation). [2]
Western Blot and Oxidative Stress Detection: Cells were lysed, and proteins were quantified. For western blot, samples were separated by SDS-PAGE, transferred to membranes, blocked, and incubated with primary antibodies (e.g., LC3B, GRP78, CHOP, 4HNE, cytochrome c, caspases, TNFα, NOX4, MnSOD) overnight, followed by HRP-conjugated secondary antibodies and chemiluminescent detection. Protein carbonylation was detected using an OxyBlot kit where protein carbonyls are derivatized with DNPH before immunodetection. [2]
Cellular Fractionation: Mitochondrial and cytosolic fractions were isolated from HK-2 cells using a mitochondrial isolation kit and differential centrifugation for subsequent analysis of compartment-specific protein localization or oxidative stress. [2]
ELISA for TNFα: TNFα secreted into cell culture media was quantified using a commercial ELISA kit following the manufacturer's protocol, involving immunocapture, washing, TMB substrate development, and absorbance measurement at 450 nm. [2]
Calcium Modulation Studies: HK-2 cells were pretreated for 45 minutes with the intracellular calcium chelator BAPTA-AM, the extracellular calcium chelator EGTA, the IP3 receptor antagonist 2-APB, or the calpain inhibitor calpeptin prior to DA exposure. Subsequent assays (MTT, western blot, calpain activity) were then performed. [2]

To assess acute lung toxicity, female Sprague-Dawley rats (200-250 g) were anesthetized with a subcutaneous cocktail of ketamine (67.5 mg/kg), xylazine (3.5 mg/kg), and acepromazine (0.66 mg/kg). While under anesthesia and placed on a heating pad, **diatrizoate sodium** nanoparticle agglomerate dry powder (10 mg) was administered via intratracheal insufflation using a dry powder insufflator with 3 mL of air. Two hours post-insufflation, rats were euthanized by isoflurane inhalation overdose, and lungs were harvested for histological examination. [1]

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To assess acute lung toxicity, female Sprague-Dawley rats (200-250 g) were anesthetized with a subcutaneous cocktail of ketamine (67.5 mg/kg), xylazine (3.5 mg/kg), and acepromazine (0.66 mg/kg). While under anesthesia and placed on a heating pad, diatrizoate sodium nanoparticle agglomerate dry powder (10 mg) was administered via intratracheal insufflation using a dry powder insufflator with 3 mL of air. Two hours post-insufflation, rats were euthanized by isoflurane inhalation overdose, and lungs were harvested for histological examination. [1]

Absorption, Distribution and Excretion
Radioactive iodine is excreted into human milk during lactation. It is currently unclear whether GLOFIL-125 is excreted into human milk. Sodium iodate has a renal clearance rate in humans very close to that of inulin. This compound is cleared by glomerular filtration and is not secreted or reabsorbed by the renal tubules. Biological Half-Life The effective half-life after infusion of iodine-125 iodate is approximately 0.07 days.

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The study provides context on clinical exposure levels. For a typical adult male (75 kg), plasma levels of iodinated radiocontrast media (RCM) like diatrizoic acid (DA) during imaging procedures are estimated to range from 4 to 15 mg I/mL, potentially reaching up to 30 mg I/mL with higher doses. [2]

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Very little iodine contrast agents injected intravenously are excreted into breast milk, and their oral absorption rate is also very low. Therefore, they are unlikely to enter the infant's bloodstream and will not cause any adverse effects on breastfed infants. Guidelines developed by multiple professional organizations indicate that breastfeeding mothers do not need to interrupt breastfeeding after receiving iodine-containing contrast agents. However, since there is currently no published experience regarding the use of iostatin during lactation, other medications may be preferred, especially when breastfeeding newborns or premature infants. ◉ Effects on Breastfed Infants
No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Non-human toxicity values
Rat intravenous LD50: 14,700 mg/kg
Mouse intramuscular LD50: 20,349 mg/kg
Mouse intravenous LD50: 1400 mg/kg
Cat intravenous LD50: 11,300 mg/kg
Dog intravenous LD50: 13,200 mg/kg

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Histological examination of lung tissue from rats two hours after intratracheal insufflation of diatrizoate sodium nanoparticle agglomerates (10 mg) showed no evidence of acute alveolar tissue damage or inflammation in both the left and right lungs. The results indicated no acute toxicity associated with the nanoparticle agglomerates or with L-leucine, the flocculating agent used in the formulation. [1]

[1]. Dry powdered aerosols of diatrizoic acid nanoparticle agglomerates as a lung contrast agent. Int J Pharm. 2010 May 31;391(1-2):305-12.

[2]. Radiocontrast Agent Diatrizoic Acid Induces Mitophagy and Oxidative Stress via Calcium Dysregulation. Int J Mol Sci. 2019 Aug 21;20(17):4074.

Sodium amidotrizoate is the sodium salt of benzoic acid, with iodine substituents at positions 2, 4, and 6, and acetamido substituents at positions 3 and 5. It is often used in combination with meglumine salt as an X-ray contrast agent for gastrointestinal examinations, angiography, and urography. It is a radiopaque contrast agent. It is an organic iodine compound and an organic sodium salt containing the sodium amidotrizoate anion.
Sodium diiodoformate is an iodinated radiopaque X-ray contrast agent. Sodium diiodoformate blocks X-rays, thus contrasting iodine-containing surface structures with iodine-free surface structures, making these areas clearly visible. This contrast agent can be used as an adjunct diagnostic agent in angiography, urography, and radiography. (NCI05)
See also: diiodobenzoic acid (with active moiety); diiodobenzoic acid meglumine; diiodotrazolium sodium (component).

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Therapeutic Use
GLOFIL-125 (sodium iostatin injection) is indicated for the diagnosis or monitoring of patients with kidney disease to assess glomerular filtration rate.Drug Warnings
Contrast Agents
As with any radioactive material, care should be taken to minimize radiation exposure for patients under appropriate patient management and to ensure that radiation exposure for occupational workers is kept to a minimum.
Rapid or bolus injections should be avoided.
Radiopharmaceuticals should only be administered by qualified physicians who are trained and have experience in the safe use and handling of radionuclides.
For more complete data on drug warnings for iostatin (out of 8), please visit the HSDB records page.

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Diatrizoate sodium is an iodinated radiocontrast agent. This study developed a dry powder aerosol formulation of diatrizoate sodium nanoparticle agglomerates for potential use as a lung contrast agent. Nanoparticles (~136 nm) were prepared by a precipitation method and then agglomerated using L-leucine into inhalable microparticles with a geometric size of ~2.4 μm, a tap density of 0.05 g/cm³, and a theoretical mass-mean aerodynamic diameter of ~1 μm. Cascade impaction studies showed the agglomerates had favorable aerosolization properties: a high emitted fraction (76-88%), a high fine particle fraction (<5.8 μm) of 93-96%, and a mass median aerodynamic diameter (MMAD) of ~1.5 μm, suitable for deep lung deposition. The formulation process yield was ~86%, and drug loading efficiency was ~85%. [1]
The study concludes that diatrizoate sodium nanoparticle agglomerates represent a promising, safe, and efficient inhalable lung contrast agent due to their improved aerosol performance and lack of acute lung toxicity in rats. [1]

C11H8I3N2NAO4

635.89

635.751

C, 20.78; H, 1.27; I, 59.87; N, 4.41; Na, 3.62; O, 10.06

737-31-5

Diatrizoic acid;117-96-4

23672589

Rhombic needles
White crystals

614.1ºC at 760 mmHg

261-262 °C (decomposes)

325.2ºC

1.926

2

4

3

21

396

0

IC1C(=C(C(C(=O)[O-])=C(C=1N([H])C(C([H])([H])[H])=O)I)I)N([H])C(C([H])([H])[H])=O.[Na+]

ZEYOIOAKZLALAP-UHFFFAOYSA-M

InChI=1S/C11H9I3N2O4.Na/c1-3(17)15-9-6(12)5(11(19)20)7(13)10(8(9)14)16-4(2)18;/h1-2H3,(H,15,17)(H,16,18)(H,19,20);/q;+1/p-1

sodium;3,5-diacetamido-2,4,6-triiodobenzoate

Diatrizoate sodium; Hypaque; MD-50; MD50; MD 50; Urovist Sodium; Triombrin

2934.99.03.00

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)

DMSO: ~100 mg/mL (~157.3 mM)

Solubility in Formulation 1: 33.33 mg/mL (52.41 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.)