Absorption, Distribution and Excretion
In rat renal cortical sections… lactate enhanced the uptake of 14C-citrinin, while probenecid (a specific anion transport inhibitor) reduced it. Dinitrophenol, both a metabolic and competitive inhibitor of anion transport, also reduced citrinin transport. Organic cations did not affect the accumulation of citrinin in the sections. These data are consistent with the view that citrinin is transported via the renal organic anion secretion system. 0.5 hours after intravenous injection of the 14C-labeled compound into rats, 14.7% and 5.6% of total radioactivity were observed in the liver and kidneys, respectively; after 6 hours, the radioactivity in the liver and kidneys decreased to 7.5% and 4.7%, respectively. The plasma concentration of 14C decreased from 9.2% at 0.5 hours to 4.7% at 6 hours. The plasma half-lives were 2.6 hours and 14.9 hours, respectively. Approximately 80% of the drug was excreted in feces and urine within 24 hours. In the second group of rats, pretreatment with 50 mg/kg citrinin via intraperitoneal injection four days prior to intravenous injection of 3 mg/kg (14)C-citrinin resulted in increased urine output. Plasma clearance curves showed two elimination rates with half-lives of 0.6 hours and 14.1 hours, respectively. In nephrotoxic rats, 7.5% of the administered radioactivity remained in the liver 24 hours after tracer administration, compared to only 1.3% in recovering rats; after 72 hours, 47% of (14)C was excreted in feces or colonic contents, compared to only 17.5% in recovering rats. In normal rats, the kidneys were clearly the primary route of excretion.
Citrin (25-50 mg/kg) has been reported to have low absorption rates in the gastrointestinal tract of rats and in the oral cavity of cats.

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Metabolism/Metabolites
Following subcutaneous injection of ¹⁴C-citrusin on day 12 of gestation, ¹⁴C-citrusin crosses the placenta in Charles River CD-1 rats. …High-performance liquid chromatography (HPLC) analysis of maternal plasma extracts revealed the presence of the maternal compound and at least one unidentified metabolite, which was more polar than the maternal compound; at least two unidentified metabolites were found in urine. Chromatography of maternal bile samples showed the presence of at least one metabolite in addition to the maternal compound, while fetal extracts contained only the maternal compound.

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Biological Half-Life
30 minutes after intravenous injection of 3 mg/kg body weight of ¹⁴C-citrusin
into Sprague-Dawley rats… two plasma elimination rates were observed with half-lives of 2.6 hours and 14.9 hours, respectively…
On day 12 of gestation, biphasic plasma elimination was also observed after subcutaneous injection of 35 mg/kg body weight of ¹⁴C-citrusin
into Charles River CD-1 pregnant rats, with half-lives of 2 hours and 40 hours, respectively.

Interactions
Citrusin inhibited the induction of localized lesions on tobacco leaves after tobacco mosaic virus inoculation. Citrusin was applied to leaves 4 or 2 hours after temperature change. Rats were orally administered 25 mg/kg citrusin or 25 mg/kg citrusin plus 1 mg/kg ochratoxin A within 24 hours of birth and sacrificed 12 days later. Neither citrusin nor ochratoxin A alone affected hepatic ATPase. Ochratoxin A and the combination therapy showed similar inhibitory effects on renal oligomycin-sensitive Mg2+-ATPase. The two mycotoxins had a synergistic effect on renal Na+-K+-ATPase. The hematological effects of weekly injections of 20 mg/kg citrusin and 5 mg/kg ochratoxin A in mice for 6 consecutive weeks were investigated. Platelet count and hematocrit significantly decreased. Spleen weight and spleen cell count decreased. In mice treated with the toxin, the total number of bone marrow cells, erythrocyte and leukocyte precursors, and megakaryocyte precursors were significantly decreased in the femoral bone marrow. Calcium concentration was also decreased.

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Non-human toxicity values
Rat intraperitoneal LD50: 67 mg/kg
Rat subcutaneous LD50: 67 mg/kg
Mice oral LD50: 112 mg/kg
Mice intraperitoneal LD50: 35 mg/kg
For more non-human toxicity values (complete data) for CITRININ (11 in total), please visit the HSDB record page.

[1]. A comprehensive review on biological properties of citrinin. Food Chem Toxicol. 2017 Dec;110:130-141.

[2]. PRESENCE OF CITRININ IN GRAINS AND ITS POSSIBLE HEALTH EFFECTS. Afr J Tradit Complement Altern Med. 2017 Mar 1;14(3):22-30.

(-)-Citrimycin is a citrinin, a metabolite of Penicillium, and the enantiomer of (+)-citrinin. Citrinin has been reported in Streptomyces argillaceus, Streptomyces kitazawaensis, and other microorganisms with relevant data. Citrinin is an antibiotic and fungal toxin derived from Aspergillus niveus and Penicillium citrinum. Mechanism of Action: This study investigated the effects of the fungal toxin citrinin on Ca2+ efflux and membrane permeability in isolated rat liver mitochondria. A higher rate of Ca2+ efflux was observed after the addition of citrinin in the presence of ruthenium red. Swelling assays showed that citrinin increased membrane permeability via a Ca2+-dependent pathway. Catalase, butylated hydroxytoluene (BHT), and dithiothreitol (DTT) did not protect against renal tubular swelling induced by Ca2+ and citrinin. In the latter set of experiments, the protective effects of ATP-Mg2+ and cyclosporine A strongly indicated pore formation. These results suggest that citrinin can induce permeability switching through a mechanism that does not involve oxidative damage. Citrinin is a secondary product of fungal metabolism and can also cause proximal tubular necrosis, but only after transport to proximal tubular cells. Both cephalosporins and citrinin utilize organic anion transporters to enter cells; these transporters are present in adult animals of all species and are likely physiologically crucial for the entry of metabolic substrates into cells. In vitro studies have shown that citrinin inhibits PAH transport in basolateral vesicles (BL), but its effect on glucose transport in the brush border (BB) remains unclear. However, in rats pretreated with citrinin (60 mg/kg, intraperitoneal injection), BL and BB membrane vesicle function was significantly reduced at 3 hours. By 16 hours, overreaction to both transport substrates had recovered, although glucose overreaction remained significantly lower than in the control group. These data indicate that citrinin... alters the function of proximal renal tubular cell membranes, and this alteration occurs relatively early after administration. This effect suggests that the membrane function changes induced by this nephrotoxic substance are an early event, or even the initiating event, in the development of acute tubular necrosis.

C13H14O5

250.2473

250.084

518-75-2

Citrinin-13C13

54680783

Light yellow to yellow solid powder

1.4±0.1 g/cm3

409.8±45.0 °C at 760 mmHg

175°C (dec.)

156.6±22.2 °C

0.0±2.2 mmHg at 25°C

1.596

1.2

2

5

1

18

536

2

C[C@@H]1[C@H](OC=C2C1=C(C(=C(C2=O)C(=O)O)O)C)C

CBGDIJWINPWWJW-IYSWYEEDSA-N

InChI=1S/C13H14O5/c1-5-7(3)18-4-8-9(5)6(2)11(14)10(12(8)15)13(16)17/h4-5,7,14H,1-3H3,(H,16,17)/t5-,7-/m1/s1

(3R,4S)-6-hydroxy-3,4,5-trimethyl-8-oxo-3,4-dihydroisochromene-7-carboxylic acid

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 (e.g. under nitrogen), 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 : ~50 mg/mL (~199.80 mM)

Solubility in Formulation 1: ≥ 1.25 mg/mL (5.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 1.25 mg/mL (5.00 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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