Absorption, Distribution and Excretion
/In/ Rat renal cortical slices ... 14C-Citrinin uptake was enhanced by lactate and reduced by probenecid, a specific inhibitor of anion transport. Dinitrophenol is a metabolic inhibitor as well as competitive inhibitor of anion transport, and it also reduced citrinin transport. Organic cations did not alter citrinin accumulation by the slices. These data are consistent with the transport of citrinin by the renal organic anion secretory system.
0.5 hr after iv administration of (14)C-labeled compound to rats, 14.7% & 5.6% of total radioactivity were observed in liver & kidneys respectively, & by 6 hr decreased to 7.5% in liver & 4.7% in kidney. Plasma concentration of (14)C decreased from 9.2% at 0.5 hr to 4.7% at 6 hr. Plasma /half-lives/ were 2.6 & 14.9 hr. Approx 80% was excreted in feces & urine by 24 hr. A 2nd group was pretreated with 50 mg/kg citrinin, ip, 4 days prior to administration of 3 mg/kg (14)C-citrinin, iv. Urine output was enhanced. Plasma disappearance curve had 2 elimination rates, with /half-lives/ of 0.6 & 14.1 hr. Nephrotoxic rats retained 7.5% of the administered radioactivity in liver compared to 1.3% in recovered rats 24 hr after tracer dose & 47% of (14)C was excreted in feces or in colon contents after 72 hr compared to 17.5% in recovered rats. In normal rats the kidneys apparently are major route of elimination.
Citrinin (25-50 mg/kg) has been reported to be poorly absorbed from the gastrointestinal tract of rats and from the mouth of cats.

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Metabolism / Metabolites
Following subcutaneous injection on day 12 of gestation, 14C-citrinin crossed the placenta in Charles River CD-1 rats. ... High-performance liquid chromatography of maternal plasma extracts revealed the presence of the parent compound and at least one unidentified metabolite, which was more polar than the parent compound; at least two unidentified metabolites were found in urine. Chromatograms of maternal bile samples suggested the presence of at least one metabolite, apart from the parent compound, whereas fetal extracts contained only the parent compound.

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Biological Half-Life
Thiry minutes after intravenous injection of 3 mg/kg bw 14C-citrinin to Sprague-Dawley rats ... . Two plasma elimination rates were observed, with half-lives of 2.6 and 14.9 h, respectively ...
After subcutaneous administration of 35 mg/kg bw 14C-citrinin to pregnant Charles River CD-1 rats on day 12 of gestation, biphasic elimination from plasma was also observed, with half-lives of 2 and 40 h, respectively.

Interactions
Citrinin inhibited local lesion induction on N. glutinosa leaves inoculated with tobacco mosaic virus. It was applied on leaves within 4 or 2 hr after the temp shift.
Rats were orally administered 25 mg/kg citrinin or 25 mg/kg citrinin plus 1 mg/kg ochratoxin A within 24 hr of birth and sacrificed 12 days later. Citrinin & ochratoxin A alone did not affect hepatic ATPase. Renal oligomycin-sensitive Mg+2-atpase was inhibited to the same degree by ochratoxin A & the combination treatment. A synergistic effect of the 2 mycotoxins was observed on renal Na+-K+-ATPase.
Hematologic effects of 6 weekly injections of 20 mg/kg citrinin & ochratoxin A (5 mg/kg) were studied in mice. The platelet count & hematocrit values decreased significantly. Weight of spleen & splenic cell count decreased. Total count of bone marrow cells, erythrocyte & leukocyte precursors, & megakaryocyte precursors of femoral bone marrow decreased significantly in toxin treated mice. Calcium concentration decreased.

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Non-Human Toxicity Values
LD50 Rat ip 67 mg/kg
LD50 Rat sc 67 mg/kg
LD50 Mouse oral 112 mg/kg
LD50 Mouse ip 35 mg/kg
For more Non-Human Toxicity Values (Complete) data for CITRININ (11 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.

(-)-citrinin is a citrinin. It has a role as a Penicillium metabolite. It is an enantiomer of a (+)-citrinin.
Citrinin has been reported in Streptomyces argillaceus, Streptomyces kitazawaensis, and other organisms with data available.
Antibiotic and mycotoxin from Aspergillus niveus and Penicillium citrinum.

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Mechanism of Action
The effects of mycotoxin citrinin on Ca2+ efflux and membrane permeabilization were studied in isolated rat liver mitochondria. The efflux rate observed in the presence of ruthenium red was higher when citrinin was added. Swelling experiments demonstrated Ca(2+)-dependent membrane permeabilization by citrinin. Catalase, butylhydroxytoluene (BHT), and dithiothreitol (DTT) did not protect swelling caused by Ca2+ plus citrinin. The protection conferred by ATP-Mg2+ and cyclosporin A in the latter experiments are strong indications of pore formation. These results suggest that citrinin can induce permeability transition by a mechanism that does not involve oxidative damage.
Citrinin, a secondary product of fungal metabolism, also produces proximal tubular necrosis, but only after transport into proximal tubular cells. Both the cephalosporins and citrinin utilize the organic anion transporter for entry into the cells, a transporter present in adult animals of all species and probably important physiologically for moving metabolic substrates into cells.
Citrinin, when studied in vitro, inhibited PAH transport /basolateral/ vesicles (BL), but had only equivocal effects on /brush border/ (BB) glucose transport. However, after pretreatment of the rats with citrinin (60 mg/kg, ip), both BL and BB membrane vesicle function was reduced markedly at 3 hr. By 16 hr, an overshoot had returned for both transport substrates, although the glucose overshoot was still significantly below control. These data demonstrate that citrinin ... alters proximal tubular cell membrane function and does so relatively early after administration to the rat. This effect suggests that alteration of membrane function by this nephrotoxicant is an early, if not initiating, event in the production 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.)