Citrinin targets multiple cellular pathways involved in toxicity and therapeutic activity. As a mycotoxin, it primarily affects kidney function and has been linked to nephrotoxicity. The compound has antibacterial activity against S. aureus including MRSA. It has antifungal, potential anticancer, and neuroprotective properties. Citrinin is an effective oral anticancer agent. Its toxic effects include nephrotoxicity and it has an LD50 of 67 mg/kg (subcutaneous or intraperitoneal in rats) and 19 mg/kg (intravenous in rabbits).

In vitro, Citrinin demonstrates antibacterial activity against S. aureus, methicillin-resistant S. aureus (MRSA), and rifampicin-resistant S. aureus. It has antifungal, potential anticancer, and neuroprotective properties. The compound is an effective oral anticancer agent. Citrinin's diverse biological activities have been characterized in various cell-based assays. Its cytotoxic effects on cancer cells and neuroprotective effects on neuronal cells have been studied. The compound's antibiotic activity was initially identified before its nephrotoxic properties were recognized.

In vivo, Citrinin is a mycotoxin that causes food contamination and has different toxic effects. It primarily affects kidney function and has been linked to nephrotoxicity. The compound has an LD50 of 67 mg/kg body-weight when given subcutaneously or intraperitoneally in rats and 19 mg/kg body-weight when given intravenously to rabbits. Citrinin is an effective oral anticancer agent. It has been studied in animal models for its toxicological effects and potential therapeutic applications.

Citrinin enzyme assays involve measuring its antibacterial, antifungal, and anticancer activities. Antibacterial activity is assessed by determining MIC against S. aureus and MRSA. Antifungal activity is evaluated using fungal cultures. Anticancer activity is assessed by measuring inhibition of cancer cell proliferation or induction of apoptosis. For toxicological studies, nephrotoxicity is assessed by measuring kidney function markers. Assays are performed in appropriate buffer systems with positive controls such as known antibiotics. IC50 values are calculated from dose-response curves.

Citrinin cell-based assays are conducted in bacterial cultures, fungal cultures, cancer cell lines, and kidney cells. Bacteria and fungi are cultured in appropriate media and treated with Citrinin at varying concentrations. Antimicrobial activity is assessed by measuring growth inhibition. Cancer cell lines are treated with Citrinin and cell viability is assessed by MTT or CCK-8 assays. Apoptosis is evaluated by Annexin V/PI staining. Nephrotoxicity is assessed in kidney cell lines by measuring cell viability and kidney function markers. Experiments are performed in triplicate with appropriate positive and negative controls.

Citrinin in vivo studies are conducted in rodent models for toxicological and therapeutic evaluation. For toxicology studies, animals are administered Citrinin at varying doses and monitored for adverse effects including nephrotoxicity. LD50 values have been determined in rats (67 mg/kg, subcutaneous or intraperitoneal) and rabbits (19 mg/kg, intravenous). For anticancer studies, tumor-bearing mice are treated with Citrinin orally. Animals are monitored for clinical signs. Tissues (especially kidneys) and blood samples are collected for histopathological and biochemical analysis. Studies are conducted in accordance with institutional animal care guidelines.

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.

Citrinin (MW 250.3 g/mol, C13H14O5) is a small molecule mycotoxin. It is soluble in DMSO and other organic solvents. The compound is stable under recommended storage conditions. Citrinin is a polyketide compound isolated from Penicillium citrinum and Monascus species. Pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution have been characterized in toxicological studies. The compound is typically used in mycotoxicology and cancer research.

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.
Citrinin is a mycotoxin with significant toxicity, particularly nephrotoxicity. It has an LD50 of 67 mg/kg (subcutaneous or intraperitoneal in rats) and 19 mg/kg (intravenous in rabbits). The compound causes food contamination and has different toxic effects. Despite its toxicity, it has antibacterial, antifungal, potential anticancer, and neuroprotective properties. The compound is intended for research use only. Standard safety precautions should be followed when handling due to its toxic nature. Comprehensive toxicological evaluation is available from mycotoxicology studies.

[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.
Citrinin is a mycotoxin originally isolated from Penicillium citrinum with diverse biological activities including antibacterial (active against S. aureus and MRSA), antifungal, potential anticancer, and neuroprotective properties. It causes food contamination and has nephrotoxic effects with an LD50 of 67 mg/kg in rats. Citrinin is an effective oral anticancer agent. It is found in Monascus species used in food production. All applications are limited to non-human research use.

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.)