Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Citrinin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2002

Citrinin production and stability in cheese.

Citrinin is a nephrotoxic fungal metabolite that has been demonstrated to be mutagenic in hepatocytes. It can be produced by several fungal species that belong mainly to the genus Penicillium and has been isolated from many feeds and human foods. Cheese is a very sensitive product because it can be naturally contaminated by citrinin-producing molds. The purpose of this study was to determine whether citrinin can be produced in cheeses and whether it is stable in these products. Both toxigenic strains of Penicillium citrinum and Penicillium expansum used were able to produce citrinin in cheese at 20 degrees C, but not at 4 degrees C. Up to 600 mg of citrinin per kg of cheese was obtained after 10 days of incubation. Interestingly, fresh goat cheese appeared to be a more favorable substrate for toxigenesis than did yeast extract-sucrose medium. Although contamination was mainly superficial, 33% of the toxin remained in cheese after trimming. Moreover, citrinin appeared to be very stable in some of the tested cheeses (goat cheese, Saint Marcellin, Soignon). For all cheeses tested, more than 50% of the initial content of citrinin was still present after 8 days of storage. Taken together, these results suggest that the contamination of cheeses by wild strains of Penicillium must be avoided.

Animals↗
PubMed1976

Combination effect of citrinin and other chemicals on rat kidney tumorigenesis.

Histological studies were made on the nephrotoxic effect of citrinin on the kidneys of rats, with or without previous treatment with the nephrotoxic chemicals, N-(3,5-dichlorophenyl)succinimide (NDPS) and N-nitrosodimethylamine (DMN). Oral administration of 0.02% or 0.05% citrinin alone caused signs of kidney injury but did not induce kidney tumors. On treatment with DMN alone, 8 of 14 rats (57.1%) developed kidney tumors; two (14.3%) were renal cell tumors, eight (57.1%) embryonal cell tumors, and one (7.1%) hemangioendothelioma. On the other hand, kidney tumors developed in 18 of 19 rats (94.7%) and 13 of 15 rats (86.7%) by the administration of 0.02% and 0.05% citrinin, respectively, after DMN. The tumors in these two groups were diagnosed histologically as renal cell tumors in 18 (94.7%) in group IV and 13 (86.7%) in group III, and as embryonal cell tumors in 14 (73.7%) in group IV and 9 (60.0%) in group III. Thus, in groups treated with citrinin after DMN the incidence of renal cell tumors was much greater and the incidence of embryonal cell tumors slightly greater than in the group treated with DMN alone. Kidney tumors developed in 4 of 18 rats (22.2%) treated with 0.02% citrinin after NDPS, but treatment with NDPS alone did not induce kidney tumors. Thus, treatment with citrinin changes the histological type and incidence of kidney tumors in rats induced by DMN. Moreover, this study confirms that citrinin in combination with NDPS can induce kidney tumor in rats, which was renal cell tumor (adenoma) histologically.

Animals↗
PubMed1995

Mechanism of citrinin-induced dysfunction of mitochondria. IV--Effect on Ca2+ transport.

The effect of citrinin on Ca2+ transport was studied in isolated kidney cortex and liver mitochondria, and baby hamster kidney cultured cells. The mycotoxin significantly inhibited the activity of 2-oxoglutarate and pyruvate dehydrogenases in both kidney cortex and liver mitochondria. Citrinin promoted a decrease in the velocity and in the total capacity of Ca2+ uptake, in both mitochondria. Apparently, citrinin acts by a mechanism similar to ruthenium red. In intact cultured cells, citrinin also had a preferential effect on mitochondrial Ca2+ fluxes. Citrinin promoted a marked decrease in the Ca2+ level in the mitochondrial matrix, whereas that of the extramitochondiral fraction became less affected. All the observed effects were dependent on the citrinin concentration.

Animals↗
PubMed1992

In vitro effects of the nephrotoxins ochratoxin A and citrinin upon biochemical function of porcine kidney.

Ochratoxin A and citrinin are nephrotoxic mycotoxins found in a variety of foods and feeds. Before studying possible interactions between these two toxins, their individual biochemical effects were examined in vitro by using renal cortical explants derived from male swine of the Hormel-Hanford strain. The following measurements were performed: macromolecule biosynthesis (protein, RNA, and DNA), respiration (14CO2 from [14C]glucose), organic ion (tetraethyl ammonium acetate, i.e., TEA) transport, and membrane perturbation (protein leakage into medium). Levels of the toxins ranged from 0.001 to 1 mM. Ochratoxin A inhibited macromolecule biosynthesis at a lower concentration (0.001 mM) than did citrinin. Protein and DNA synthesis were particularly sensitive to ochratoxin A. Syntheses of protein and DNA were inhibited at ochratoxin A concentrations of 0.01 and 0.001 mM, respectively. RNA synthesis was less sensitive to the mycotoxin; it was inhibited only 60% at 1 mM, the highest concentration of ochratoxin A tested. Citrinin levels of 0.01 mM were required for inhibition of RNA, DNA, and protein synthesis. Inhibition by citrinin was approximately equal for all three classes of macromolecules. Citrinin was more effective than ochratoxin A in the inhibition of respiration and TEA transport; the minimum effective levels of citrinin were 1 and 0.01 mM, respectively. Serious membrane damage as evidenced by increased protein leakage was not caused by either toxin. Stimulation of respiration, perhaps reflective of uncoupling of oxidative phosphorylation, was produced by an ochratoxin A concentration of 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Transport of citrinin by rat renal cortex.

Citrinin, a secondary product of fungal metabolism, is nephrotoxic in the rat. Because citrinin is an organic anion, it might be expected to be transported by the renal organic anion transport system. Rat renal cortical slices were used to characterize the transport. 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.

Animals↗
PubMed1991

The effects of potassium chromate and citrinin on rat renal membrane transport.

Both chromate and citrinin have been shown to produce acute renal damage. Although both substrates act on the proximal tubule in the rat, they affect different parts of that nephron segment. As with most nephrotoxicants, the mechanism(s) or subcellular target(s) for citrinin or chromate is unknown. The availability of methodology for isolation of functional membrane vesicles has afforded the opportunity to study the plasma membrane as a target for the effects of citrinin and chromate. Whether studied solely with in vitro conditions or after administration to the rat, chromate exhibited its primary action on the basolateral (BL) membrane vesicles. This was exhibited by a reduction in the p-aminohippurate (PAH) overshoot. At both 3 and 16 hr after treatment (40 mg/kg, sc) there was a significant, but relatively modest, effect on glucose transport by brush border (BB) vesicles. Citrinin, when studied in vitro, inhibited PAH transport (BL vesicles), but had only equivocal effects on 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 both citrinin and chromate alter proximal tubular cell membrane function and do so relatively early after administration to the rat. This effect suggests that alteration of membrane function by these nephrotoxicants is an early, if not initiating, event in the production of acute tubular necrosis.

Animals↗
PubMed1982

Embryocidal, teratogenic and fetotoxic effects of citrinin in rats.

Citrinin, a fungal metabolite produced by several species of Penicillium and Aspergillus, has been found to contaminate foods used by animals and man. Citrinin is nephrotoxic and has been implicated in disease outbreaks in animals and humans. In this study the teratogenicity, embryotoxicity, and fetotoxicity of citrinin was determined in Sprague-Dawley rats after subcutaneous administration of a single dose of 35 mg/kg on gestation day 3, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. Dams so treated lost weight for 2 days following administration. Subsequently, weight gain for treated animals was similar to that for controls. Relatively high maternal mortalities also were associated with this pretreatment regimen. Treatment with 35 mg/kg on certain days of gestation resulted in deaths of one half or more of the pregnant dams. No significant effects of citrinin were observed on the number of implants. Resorption of implants, however, was higher in treated animals than controls when dams were treated on days 6, 7, 8, 10, 11 or 12 of gestation. Fetuses from dams given citrinin were significantly smaller than those from controls by about 22% on average. No major gross or skeletal malformations were found in fetuses born to mothers which received citrinin. Major internal soft tissue malformations seen were enlarged kidneys, internal hydrocephalus and cleft palate.

Animals↗
PubMed1982

Disposition and metabolism of [14C]citrinin in pregnant rats.

Citrinin is a product of fungal metabolism capable of producing nephrotoxicity. Distribution, excretion and metabolism of [14C]citrinin was studied in pregnant female rats after subcutaneous administration of 35 mg/kg on the 12th day of gestation. Elimination of [14C]citrinin-derived radioactivity from plasma was biphasic. The half-lives for the rapid (alpha) and slower (beta) phases of elimination were 1.95 h and 39.7 h, respectively. Approximately 74% of the radioactivity appeared in the urine in the first 24 h, with only 1.7% and 1.4% in the urine at 48 h and 72 h, respectively. Fecal elimination accounted for 9.5%, 4.1% and 7.3% of the total radioactivity at each of these times. At least one metabolite of citrinin was demonstrable with high performance liquid chromatography (HPLC) of plasma extracts. Retention times for the parent compound and metabolite were 270 s and 175 s, respectively. The metabolite was more polar than the parent compound. At least 2 metabolites of citrinin were found in urine of the same rats. Retention times for two metabolites were 140 s and 180 s, with both metabolites more polar than the parent compound. Chromatograms of bile samples suggested at least one metabolite was present with a retention time of 140 s. Chromatograms of uterus extracts indicated the presence of one metabolite with a retention time of 180 s. Chromatograms of fetus extracts indicated that no metabolites of citrinin were present.

Animals↗
PubMed1996

Citrinin produces acute adverse changes in renal function and ultrastructure in pentobarbital-anesthetized dogs without concomitant reductions in [potassium]plasma.

Citrinin's nephrotoxicity was examined in pentobarbital-anesthetized dogs under conditions that minimized or avoided significant changes in a number of its actions that could indirectly and adversely affect renal function and ultrastructure, such as, (i) major acute reductions in blood pressure and renal blood flow and, (ii) emesis and diarrhea that could lead to dehydration and electrolyte imbalances, especially hypokalemia. Slow intravenous injection of 20 mumol citrinin/kg to pentobarbital-anesthetized dogs did not induce any alterations in renal tissue ultrastructure or in any of the 23 whole blood, plasma or renal function parameters that were monitored over a 6-h post-citrinin period. On the other hand, 80 mumol citrinin/kg produced significant increases in the hematocrit and in the renal excretion rates of protein and glucose; modest reductions were noted in CIN, RBF and excretion rate of inorganic phosphorus. In addition, 80 mumol citrinin/kg induced ultrastructural lesions in the cells of the S2 proximal tubular segment, the thick ascending limb, the distal convoluted tubule and the collecting ducts. The glomeruli, S1 and S3 cells of the proximal tubule and the thin descending and ascending limbs of Henle's loop were unaffected by both citrinin doses. The location and nature of the adverse ultrastructural lesions were most likely the result of the direct actions of citrinin (or a citrinin metabolite) since the effects of citrinin that could lead to indirect adverse renal effects were totally avoided or greatly minimized.

Anesthesia, Intravenous↗
PubMed1990

Rapid and sensitive detection of citrinin production during fungal fermentation using high-performance liquid chromatography.

A rapid and sensitive assay was developed for the detection of the mycotoxin citrinin by reversed-phase chromatography. Citrinin was eluted from a radical-compression C18 column with a retention time of 3.86 min (flow-rate of 2.5 ml/min) with acetonitrile-water-acetic acid (40:59:1) containing tetrabutylammonium phosphate (0.0025 M) [corrected]. Comparative analysis revealed fluorescence detection to be 100 times more sensitive than detection by conventional ultraviolet absorbance. The fluorescence excitation and emission maxima of citrinin were 330 and 500 nm, respectively. The assay was linear over the concentration range between 0.01-100 micrograms/ml. Recovery experiments conducted by addition of citrinin to fermentation samples, revealed the assay quantitation efficiency to be 91-102%. Assay utility was demonstrated by using an Aspergillus niveus culture, propagated in complex liquid medium. Citrinin production was detected as early as 20 h following inoculation and increased dramatically when the culture entered the stationary phase of growth, analogous to other secondary metabolites. Unlike previously reported methods, this procedure has the advantage of enabling the direct quantitative analysis of citrinin in crude microbial fermentations without sample extraction.

Aspergillus↗
PubMed1999

Mutagenicity of commercial Monascus fermentation products and the role of citrinin contamination.

Pigments produced as secondary metabolites by various isolates of moulds belonging to the genus Monascus have been used traditionally as colorants in Oriental food. Modern food industry has rediscovered these moulds as promising source for natural colorants. However, recent studies evidence that one of the secondary metabolites produced by Monascus is identical in structure to the mycotoxin citrinin. Thus, a sensitive HPLC method was developed to analyse these food colorants for contamination with citrinin. The mycotoxin could be detected in all the commercial Monascus samples at concentrations varying between 0.2 to 17.1 microg/g. In addition, the mutagenicity of commercial Monascus samples applying Salmonella-microsome assay and Salmonella-hepatocyte-assay was investigated and compared to the results obtained with citrinin. Citrinin and two Monascus extracts induced a positive dose depending mutagenic response in the Salmonella-hepatocyte-assay applying strain TA-98. However, no mutagenicity could be detected in the Salmonella-microsome assay, neither with nor without S9-mix, for citrinin and Monascus extracts, applying TA-98, TA-100, TA-1535, TA-1538 and TA-97. These findings provide further evidence that citrinin requires complex cellular biotransformation to exert mutagenicity.

Animals↗
PubMedDate not supplied

Pigments and citrinin biosynthesis by fungi belonging to genus Monascus.

Citrinin is a mycotoxin, which is produced by fungi belonging to the genus Monascus, known in biotechnology as producers of azaphilone pigments. The relation between biosynthesis of these secondary metabolites was investigated in different species of the genus Monascus in batch-culture at the following cultivation conditions: T = 28 degrees C, agitation 220 rpm, and a medium, which induce citrinin production, containing ethanol as a carbon source. The screening was carried out with 16 fungal strains and the biosynthesis of citrinin and pigments was monitored quantitatively at the standard conditions mentioned above. Some kinetic parameters of the process have been determined. The values of the growth yield coefficient Y(X/C) were between 0.32 and 0.57. The amount of the extracellular red and orange pigments at the end of cultivation varied for the different strains between 0.09 and 1.33 OU/ mg dry weight, and 0.15 and 0.96 OU/mg dry weight, respectively. The amount of the total pigments measured was between 0.16 and 3.6 OU/mg dry weight, and between 0.21 and 3.39 OU/mg dry weight. The determined ratio 500 nm/400 nm, characterizing the pigment production, ranged between 0.60 and 1.06. Twelve of the investigated strains produced citrinin and pigments, two of them produced only pigments. Two strains were not able to produce neither pigments nor citrinin. Thus, the biosynthesis of citrinin appeared to be strain-specific and does not correlate with the pigments' biosynthesis by the fungal strains belonging to the genus Monascus.

Anti-Bacterial Agents↗
PubMed1985

Effect of heat drying of corn on the extraction of citrinin.

Experiments were conducted to determine if drying citrinin-contaminated corn at varying temperatures and times either bound citrinin or converted it to a derivative that could not be extracted from the grain. Sterilized whole corn was inoculated with spores of a Penicillium spp. that produces citrinin and was incubated for 8 weeks. Following incubation, the corn was mixed and divided into three portions. In Experiment 1, one portion was dried at room temperature and the other portions were dried at 65 C for either 40 or 72 hr. In Experiment 2, one portion was air-dried and the other portions were dried at 60 C for 24 hr or 100 C for 3 hr. The corn was then ground to a texture suitable for feeding to chicks. Analysis of the corn indicated that temperature or length of drying time had no adverse effects on the extraction of citrinin from the corn. The citrinin was not rendered unextractable by either being bound because of heating or by being converted to a derivative. When fed to chicks for 5 hr, water consumption and urine excretion data indicated that there was no loss of citrinin activity because of method of drying.

Animal Feed↗
PubMed2026

Chromosome-Scale Genome Analysis Reveals Locus-Specific Disruption of the Citrinin-Associated Region in a Furu-Derived Monascus ruber Strain BC20.

Monascus species are widely used in traditional fermented foods for pigment and flavor formation, but citrinin contamination remains a major safety concern that limits broader food applications. Therefore, this study aimed to evaluate the citrinin risk of a furu-derived Monascus ruber strain, BC20, by integrating phenotypic screening across food-relevant matrices with genome-resolved analysis. After 14 days of cultivation across eight matrices, including fungal media as well as dairy-, cereal-, and bran-based substrates, citrinin was not detected by immunoaffinity cleanup combined with HPLC-FLD (LOD, 4 μg/kg; LOQ, 12 μg/kg). To investigate the genetic basis of this phenotype, we generated a chromosome-scale genome assembly for BC20 and conducted comparative analyses across a total of 19 Monascus genomes. ANI analysis and phylogenomic inference consistently placed BC20 within the ruber-pilosus clade. Comparative synteny analysis showed that the citrinin-associated locus in BC20 no longer retained an intact cluster configuration but instead exhibited a remnant-locus architecture, and similar patterns were also observed in several related genomes from the same clade. By contrast, the monacolin K (mk) locus remained syntenically conserved in BC20, supporting locus-specific structural disturbance rather than assembly-derived pseudo-absence. Additionally, its antifungal susceptibility was determined. Overall, BC20 represents a M. ruber candidate strain with undetectable citrinin, and this study provides a practical analytical framework for citrinin risk screening in food-related Monascus isolates.

biosynthetic gene cluster↗
PubMed1998

Citrinin-induced mitochondrial permeability transition.

The effects of mycotoxin citrinin on Ca2+ efflux and membrane permeabilization were studied in isolated rat liver mitochondria. The efflux rate observed when in presence of ruthenium red was higher when citrinin was added. Swelling experiments demonstrated Ca(2+)-dependent membrane permeabilization by citrinin. Catalase, butylhydroxitoluene (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.

Animals↗
PubMed1995

Citrinin affects the oxidative metabolism of BHK-21 cells.

The effects of citrinin on energy production along the respiratory chain and on glycolytic lactate production were examined in BHK-21 cultured cells. Citrinin inhibited the oxygen consumption rate by about 45 per cent. The respiratory rate of digitonin-treated cells energized with succinate, in the presence of ADP, was reduced by about 39 per cent. The mycotoxin inhibited the glucose utilization of BHK-21 cells by about 86 per cent. Cells treated with citrinin produced a small quantity of pyruvate, but were unable to produce lactate. It is concluded that BHK-21 cells cannot generate lactate when oxidative metabolism is inhibited by citrinin. The perturbations in BHK-21 cells caused by citrinin are due to alterations in mitochondrial function and in the glycolytic anaerobic pathway.

Animals↗
PubMed2006

Biotransformation of citrinin to decarboxycitrinin using an organic solvent-tolerant marine bacterium, Moraxella sp. MB1.

Organic solvent tolerant microorganisms (OSTMs) are novel group of extremophilic microorganisms that have developed resistance to withstand solvent toxicity. These organisms play an important role in biotransformation of organic compounds. In the present study, we used an organic solvent-tolerant marine bacterium, Moraxella sp. MB1. 16S rRNA sequencing revealed that the bacterium shows 98% similarity with an uncultured marine bacterium with GenBank accession no. AY936933. This bacterium was used for the transformation of a toxin, citrinin, into decarboxycitrinin in a biphasic system. This transformation was affected by decarboxylase enzyme produced by MB1. Transformation of citrinin to decarboxycitrinin was monitored by thin-layer chromatography (TLC) and spectrophotometrically. Citrinin decarboxylase activity responsible for transformation was studied in cell-free growth medium and cell lysate of Moraxella sp. MB1. Citrinin decarboxylase was found to be intracellular in nature. The biotransformed product was purified and identified as decarboxycitrinin using electrospray ionization mass spectrometry (ESI-MS/MS) and nuclear magnetic resonance (NMR) spectrometry. The antibiotic activity of both citrinin and decarboxycitrinin is also reported.

Anti-Bacterial Agents↗
PubMed2003

Improvement of monacolin K, gamma-aminobutyric acid and citrinin production ratio as a function of environmental conditions of Monascus purpureus NTU 601.

Monascus, a traditional Chinese fermentation fungus, is used as a natural dietary supplement. Its metabolic products monacolin K and gamma-aminobutyric acid (GABA) have each been proven to be a cholesterol-lowering drug and a hypotensive agent. Citrinin, another secondary metabolite, is toxic to humans, thus lowering the acceptability of red mold rice to the general public. In this study, the influence of different carbon and nitrogen sources, and fatty acid or oils, on the production of monacolin K, citrinin and GABA by Monascus purpureus NTU 601 was studied. When 0.5% ethanol was added to the culture medium, the production of citrinin decreased from 813 ppb to 561 ppb while monacolin K increased from 136 mg/kg to 383 mg/kg and GABA increased from 1,060 mg/kg to 7,453 mg/kg. In addition, response surface methodology was used to optimize culture conditions for monacolin K, citrinin and GABA production, and data were collected according to a three-factor (temperature, ethanol concentration and amount of water supplemented), three-level central composite design. When 500 g rice was used as a solid substrate with 120 ml water and 0.3% ethanol, the production of monacolin K at 30 degrees C increased from 136 mg/kg to 530 mg/kg, GABA production increased from 1,060 mg/kg to 5,004 mg/kg and citrinin decreased from 813 ppb to 460 ppb.

Carbon↗