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At least 19 recordsLinked to original sources

PubMed1987

Avian diuretic response to renal portal infusions of the mycotoxin citrinin.

Citrinin is a nephrotoxic mycotoxin produced by common molds. Previous research has shown that citrinin causes increased urine flow, increased free water clearance, and increased sodium, potassium, and inorganic phosphate excretion. The present study was conducted to evaluate the dose-response effects of citrinin and to further evaluate previously reported phosphaturic effects of citrinin. Ureteral urine was collected from anesthetized domestic fowl during a control period (30 min) and during unilateral renal portal infusion (90 min) of citrinin carrier vehicle, 200 ppm citrinin, or 400 ppm citrinin. Comparisons of the portal infused vs. uninfused kidneys were used to evaluate the direct effects of citrinin. Citrinin caused acute (unilateral) dose-related increases in urine flow, free water clearance, and fractional sodium excretion and dose-related decreases in urine osmolality. Citrinin had no direct effect on glomerular filtration rates, fractional potassium excretion, or fractional inorganic phosphate excretion. An additional group of birds received systemic intravenous infusions of parathyroid hormone (PTH) beginning 40 min after the start of unilateral renal portal infusion of citrinin. The citrinin and PTH infusion were continued for 60 min. Fractional inorganic phosphate excretion increased bilaterally during the citrinin-PTH infusion period but citrinin had no direct phosphaturic effect. Previously reported phosphaturic effects of citrinin were not confirmed in the present study.

Animals↗

PubMed1987

Citrinin toxicity in young chicks.

Two experiments were conducted to demonstrate the capacity of citrinin to cause dose-related increases in water consumption and urine excretion. In Experiment 1, chicks 24 days old were fed mixtures of untreated and inoculated corn containing citrinin to provide 0, 50, 100, 150, 200, and 250 micrograms of the toxin per gram of blended corn. The corn was fed for 4 hr, and water intake and urine excretion were measured. Chicks consumed 0, 1.23, 2.37, 3.68, 4.26 and 5.44 mg citrinin from the respective treatments. Compared with chicks consuming no citrinin, water intake and urine excretion of treated chicks increased (P less than .05) when chicks consumed 3.68 mg or more citrinin. Measures of the difference between water intake and urine excretion were similar for all treatments except for chicks consuming 3.68 mg citrinin; for those chicks the difference was significantly greater (P less than .05) than for chicks consuming 1.23 mg citrinin. In Experiment 2, inoculated corn was heated in a microwave oven for 1, 2, 8, and 16 min. Temperatures of the heated corn samples, when removed from the oven, were 76 C, 100 C and 105 C, respectively. Chicks that were 28 days old were fed these various samples of corn for 4 hr. Heating corn for 2 min to a temperature of 76 C caused no apparent loss of citrinin activity based on water intake and urine excretion measures. Heating the corn for 8 min to a temperature of 100 C destroyed some of the citrinin activity. Heating citrinin-contaminated corn to 105 C for 16 min destroyed the diuretic effect of the mycotoxin.

Animals↗

PubMed1989

Effects of chronic ochratoxin A and citrinin toxicosis on kidney function of single comb White Leghorn pullets.

The objectives of the present study were to examine the effects of repeated or chronic ochratoxin A (OA) and citrinin exposure, and to determine if severe ochratoxicosis permanently alters renal function in pullets. The OA-treated birds were injected intramuscularly (breast muscle) with a 1 mg/mL solution of OA at a dose of .25 mg/kg BW or .5 mg/kg BW. Citrinin-treated birds were injected with a 6 mg/mL solution of citrinin at a dose of 6 mg/kg BW. Control birds received an equal volume injection of the citrinin and OA solvent, 100% ethanol, at a dose of 1 mL/kg BW. Kidney function was evaluated after 10 consecutive days of OA, citrinin, or ethanol injection, and 2 wk following the final injections. Venous blood gas measurements were taken after the seventh day of injection. The OA increased urine flow rate, decreased urine osmolality, increased ion excretion (Na, K, Ca, P), increased water consumption, increased manure moisture, and caused a relative alkalosis when measured immediately after 10 days of OA injection. These effects of OA were not detected 2 wk later. Citrinin increased manure moisture, decreased plasma P, increased the clearance of para-aminohippuric acid, and had no consistent effect on blood acid-base parameters. The results suggest that OA may cause an osmotic diuresis by inhibiting tubular reabsorption of electrolytes. The data also suggests that the effects of OA may be reversible simply by discontinuing toxin administration. Although the citrinin-induced increase in manure moisture indicates that citrinin had an effect on renal function, renal function analysis suggests that even repeated exposure to high doses of citrinin may only have a short duration of diuretic action on the kidneys.

Analysis of Variance↗

PubMedDate not supplied

Distribution and excretion of [14C]citrinin in rats.

The distribution and excretion of radioactivity from [14C]citrinin (3 mg/kg, i.v) was determined in male rats. At 0.5 h after administration maximum values of 14.7% and 5.6% of total radioactivity were observed in the liver and kidneys, respectively, and by 6 h decreased to 7.5% in the liver and 4.7% in the kidney. Plasma concentration of 14C decreased from 9.2% at 0.5 h to 4.7% at 6.0 h. 2 plasma elimination rates were observed, with half-lives of 2.6 and 14.9 h, respectively. Approximately 80% of the administered 14C activity was excreted in feces and urine by 24 h after administration. A second group of rats was pretreated with 50 mg/kg of citrinin, i.p., 4 days prior to administration of 3 mg/kg [14C]citrinin, i.v. 30% of the pretreated animals died and the remaining animals were divided into 2 groups on day 4 after pretreatment; rats which were "nephrotoxic" and rats which had "recovered" from the initial insult of citrinin. Proteinuria and glucosuria as well as enhanced urine output were observed in "nephrotoxic" rats 4 days after pretreatment. 24 h after [14C]citrinin, only 13% of 14C activity was detected in the urine of "nephrotoxic" rats. The plasma disappearance curve had 2 elimination rates, with half-lives of 0.6 and 14.1 h. "Nephrotoxic" rats retained 7.5% of the administered radioactivity in the liver compared to 1.3% in the "recovered" rats 24 h after the tracer dose and 47% of the radioactivity was either excreted in feces or in the colon contents after 72 h compared to 17.5% in "recovered" rats. Extraction of urine samples from "nephrotoxic" and "recovered" rats with chloroform suggested increased water soluble metabolites of citrinin in the urine from "nephrotoxic" rats. These data also suggested that in normal rats the kidneys are the major route of elimination of citrinin and its metabolite(s) while in rats rendered nephrotoxic by citrinin pretreatment, elimination is more dependent on hepatic excretion.

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↗

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↗

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↗

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↗

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↗

PubMed1988

Temperature influence on Penicillium citrinum thom growth and citrinin accumulation kinetics.

To study the temperature influence on both Penicillium citrinum growth and citrinin accumulation, a 20, 25 and 30 degrees C. Radial and 30 degrees C. Radial growth rate and lag phase were determined from the increase in colony diameter with time. The optimal temperature for P. citrinum growth was 30 degrees C. Citrinin extracted from the agar medium was determined by thin layer chromatography. Citrinin accumulation kinetics were analyzed by fitting the data to curves generated by using a logistic function. The parameters obtained from this equation demonstrated, for all temperatures studied, that the maximum citrinin accumulation by P. citrinum on Czapek agar with maize extract was at about 30 degrees C. At 37 degrees C a rapid decrease in the citrinin concentration was observed after a maximal value was reached.

Agar↗

PubMed1977

The mechanism of action of citrinin on rabbit kidney alkaline phosphatase activity in vivo.

The effect of citrinin poisoning on rabbit kidney alkaline phosphatase was investigated. After seven days administration of citrinin (2 mg/kg body weight daily) the animals were sacrificed and the level of enzymes estimated in serum and kidney. Serum enzymes showed no variation in activity in the citrinin-treated animals, but in kidney, alkaline phosphatase activity decreased significantly. The decreased activity was mainly associated with the cytoplasmic fraction and in fractions Ib and II. The enzyme II obtained from citrinin-treated animal showed no kinetic difference in substrate specificity, inhibition by phenylalanine, phosphate, sodium-EDTA and Zn2+ ions, activation by Mg2+ ions, thermal inactivation and electrophoretic mobility to that of control Enzyme II. Immunological studies showed that the decrease in enzyme activity was due to existence of inactive enzyme protein. Hormones like cyclic AMP, prostaglandin E1 and parathyroid hormone reversed the decreased enzyme activity due to citrinin poisoning in mouse and rabbit. This study favours the possible existence of active and inactive forms of alkaline phosphatase in the system.

Alkaline Phosphatase↗

PubMed1977

Ochratoxin A and citrinin induced nephrosis in Beagle dogs. I. Clinical and clinicopathological features.

Ochratoxin A and citrinin, both mycotoxins, were given separately and combined to young Beagle dogs for 14 days. Ochratoxin A, 0.1 and 0.2 mg/kg, was given by capsule, and citrinin, 5 and 10 mg/kg, was dissolved in ethanol and given by intraperitoneal injection. Clinical signs of toxicosis in dogs given 10 mg/kg citrinin and the higher combined doses included anorexia, retching, tenesmus, weight loss, prostration and death. Severity of the clinical disease and mortality were increased when the mycotoxins were combined, which indicated synergism. The clinicopathological abnormalities reflected renal damage, in that glutamic oxaloacetic transaminase and lactic dehydrogenase increased in the urine of the dogs with clinical signs of poisoning. Serum lactic dehydrogenase was increased in dogs given 10 mg/kg citrinin. Cellular and granular casts, ketones, protein and glucose were in the urine of dogs given large doses of citrinin alone or combined with ochratoxin A. Serum concentrations of sodium, potassium and chloride in the dogs given high doses of each group.

Animals↗

PubMed1977

Ochratoxin A and citrinin induced nephrosis in Beagle dogs. III. Terminal renal ultrastructural alterations.

The extent and type of renal ultrastructural changes in Beagle dogs varied with the administration of ochratoxin A and citrinin alone and in the two dosage combinations. The three predominant changes were cytoplasmic vacuolation, myelin figure formation and lesions designated as cytoplasmic disarray. These changes were mainly of the endomembane system of the tubular epithelial cells. Cytoplasmic vacuoles were within proximal and distal tubules and collecting ducts and were most numerous in dogs given 10 mg/kg critrinin. Vacuolation of similar distribution, but less severe, was seen in renal tubular cells of dogs given the higher dose of the combined mycotoxins (0.2 mg/kg ochratoxin A + 10 mg/kg citrinin). This damage was limited to the proximal tubular cells in dogs given only ochratoxin A (0.1 or 0.2 mg/kg). Myelin figures were in proximal epithelial cells of dogs given ochratoxin A alone or combined with citrinin. There was cytoplasmic disarray in dogs of all groups except for dogs given 5 mg/kg citrinin. This lesions was usually limited to the proximal tubules. The lesions, however, was found in cells of the distal tubules of dogs given 10 mg/kg citrinin alone.

Animals↗

PubMed1988

Effects of ochratoxin A alone and in combination with citrinin on kidney function of single comb White Leghorn pullets.

The present study was designed to evaluate the acute effects of ochratoxin A (OA) on pullet renal function, and to determine if the diuretic effects of citrinin are altered by acute ochratoxicosis. Birds were injected intramuscularly with a 1-mg/mL solution of OA at a dose of 5 mg/kg body weight for 2 consecutive days. Control birds received an equal volume injection of the OA carrier vehicle (100% ethanol). On the 3rd day, birds were anesthetized and prepared for renal function studies. Following 30 min of control urine and plasma collection, an intravenous infusion containing 400 ppm citrinin was initiated, and urine and plasma were collected for an additional 70 min. The OA alone caused an increase in manure moisture and increased hematocrits (hemoconcentration), but direct effects on glomerular filtration rate (GFR), urine flow rate/GFR, para-aminohippuric acid clearance (CPAH), free water clearance (FWC), and electrolye excretion (Na, K, Ca, P) were not consistently demonstrated. The OA may cause hemoconcentration by causing a subtle increase in urine flow (diuresis), or by increasing intestinal water loss (diarrhea). Citrinin infusion caused increased urine flow rate, increased urine flow rate/GFR, increased FWC, increased Na excretion, and decreased urine osmolality. Pretreatment with OA attenuated these effects of citrinin, presumably due to renal compensation for the OA-induced hemoconcentration. Citrinin and OA do not appear to have additive diuretic effects during the first 48 h of toxin exposure.

Animals↗

PubMedDate not supplied

Effects of citrinin on renal tubular transport functions in the rat.

The fungal toxin, citrinin, has been implicated as a nephrotoxin. Both in vitro and in vivo studies were undertaken to examine, in a controlled laboratory setting, the effects of citrinin on overall renal function as well as on specific renal transport processes. At a dose of 70 mg/kg citrinin caused an increase in urine production and a decrease in urine osmolality in the Sprague-Dawley rat. Maximal effects were observed at 4 days after a single dose, and animals surviving for that time period regained normal renal function by 5--8 days. Animals that failed to survive first entered a period of oliguria or anuria. Fischer 344 rats did not demonstrate an unusual sensitivity to citrinin. Renal slice transport of various organic compounds, e.g., paminohippurate (PAH) and tetraethylammonium (TEA), also was inhibited with maximal effects seen at day 4. In vitro effects of citrinin on fresh renal tissue were different, in part, from the effects seen with pretreatment. No alterations of renal cortical inorganic electrolytes were observed.

Animals↗

PubMed1976

Antiprotozoal activity in citrinin.

Citrinin has an inhibitory effect on growth of T. pyriformis. Citrinin also caused a shift to smaller cell size, particularly at the higher concentrations (25, 50 and 100 mug/ml). The mycotoxin exerted only a marginal effect on the respiration of T. pyriformis; but citrinin (25 mug/ml) induced an inhibitory effect on DNA, RNA and protein content. The greatest decrease was in RNA, while smaller decreases in protein and DNA were observed. A bioassay employing T. pyriformis was determined; the lower limit of citrinin detection was between 1 and 5 mug/ml.

Animals↗

PubMed1979

Activity of citrinin metabolized by rat and human microsome fractions in clastogenicity and SCE assays on Chinese hamster V79-E cells.

The mycotoxin citrinin is a potent inducer of chromosomal aberrations in the clastogenicity assay on V79-E cells when metabolized by rat and human liver microsomes. Rat and human liver microsomes, standardized on protein content, activate citrinin at equal levels. 5 X 10(-4) M citrinin induces complex translocations in a high frequency as well as defects of chromosomal coiling. Higher concentrations are cytotoxic, lower ones are almost inactive. After metabolization of mycotoxin by rat-kidney microsomes or an S9 mix fraction containing rat liver and kidney microsomes, toxic effects predominate and chromosomal aberrations are diminished. Clastogenic citrinin concentrations do not induce an increase of SCE frequency. Although the mode of action of this mycotoxin on chromosomal structure remains obscure, possible explanations are discussed.

Animals↗

PubMedDate not supplied

Inhibition of RNA- and DNA-synthesis by citrinin and its effects on DNA precursor-metabolism in V79-E cells.

1. The RNA synthesis of V79-E cells was inhibited by the mycotoxin citrinin time- and concentration-dependently. 2. Among the different RNA species mainly the rRNA synthesis was found to be inhibited by 200 microM citrinin. 3. At different precursor concentrations DNA synthesis was inhibited by citrinin after 30 min at least whereas labelling of the acid soluble fractions was found to be 3-fold higher than in untreated cells. 4. Remarkable perturbation of the DNA precursor metabolism, including release of precursor into the medium, was found to occur during citrinin treatment.

Animals↗