Citrinin--a fungistatic antibiotic and narrowing factor.
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In the present work we studied the antifungal effect of eugenol and thymol on the growth and production of citrinin from Penicillium citrinum (NRRL 2274 and NRRL 2269) in culture media and in different Spanish cheeses (Arzúa-Ulloa, Cebreiro and San Simón). The rate of growth was assessed by measuring colony diameters and the production of citrinin was measured using a rapid semi-quantitative fluorometric technique confirmed by RP-HPLC. A stronger inhibitory effect of eugenol than thymol was evident. 200 microg/ml of eugenol in solid culture medium increased the lag time of growth up to 9 days, and decreased the rate of colony growth. In liquid medium, a complete inhibition of fungal growth was observed. By contrast, thymol in the liquid culture medium only affected the growth rate. In Arzúa-Ulloa cheese, 200 microg/ml of eugenol fully inhibited fungal growth, while in Cebreiro cheese no effect was observed for this compound. Regarding the capacity to inhibit mycotoxin production 100 microg/ml eugenol delayed citrinin production until the sixth day, after which a limiting effect persisted. In Arzúa-Ulloa cheese, no citrinin was detected at a concentration of 150 microg/ml of eugenol, but citrinin was detected after 5 days in the case of thymol at the same concentration. In Cebreiro cheese, neither eugenol nor thymol prevented the production of citrinin at the concentrations applied.
Citrinin and ochratoxin A disrupt renal function in many animal species. The mechanism(s) underlying these actions is (are) unclear. Although citrinin has been shown to bind covalently to renal tissue, there also is evidence that it is active in the unmetabolized form. Altered calcium homeostasis has been suggested as an event which might mediate cell injury and/or death; a possible role for calcium in citrinin- or ochratoxin A-induced nephrotoxicity is reported here. Renal cortical slice calcium balance was monitored by the uptake of 45Ca. Either ochratoxin A or citrinin added to fresh renal cortex slices enhanced 45Ca accumulation. These effects were evident as early as 5 min after addition of the toxins. Greater 45Ca uptake occurred with bathing solution calcium concentration of 1.1 mM than in the absence of added carrier calcium. Finally, the effect of citrinin to reduce p-aminohippurate accumulation by renal cortical slices was greater in the presence of calcium than in its absence.
Penicillium citrinum VKM F-1079 was found to produce clavine ergot alkaloids and citrinin, a secondary O-heterocyclic metabolite. Citrinin was produced in the idiophase, whereas the production of ergot alkaloids paralleled fungal growth. The addition of manganese ions to the growth medium stimulated the biosynthesis of both citrinin and ergot alkaloids. Zinc ions stimulated only citrinin synthesis. The presence of these microelements in the growth medium influenced the proportion between the ergot alkaloids synthesized. Copper, manganese, and iron ions affected but little fungal growth and alkaloid production. The effect of microelements on the main kinetic parameters of growth and alkaloid production was studied.
Penicillium expansum is known for its destructive rot and patulin production in apple juice. According to the literature, P. expansum can, among other compounds, produce citrinin, ochratoxin A, patulin, penitrem A, and rubratoxin B. In this study the qualitative production of metabolites was examined using TLC (260 isolates), HPLC (85 isolates), and MS (22 isolates). The results showed that none of the 260 isolates produced ochratoxin A, penitrem A, or rubratoxin B. However, chaetoglobosin A and communesin B were produced consistently by all 260 isolates. Patulin and roquefortine C were produced by 98% of the isolates. Expansolides A/B and citrinin were detected in 91 and 85% of the isolates, respectively. Chaetoglobosins and communesins were detected in naturally infected juices and potato pulp, whereas neither patulin nor citrinin was found. Because most P. expansum isolates produce patulin, citrinin, chaetoglobosins, communesins, roquefortine C, and expansolides A and B, foods contaminated with this fungus should ideally be examined for chaetoglobosin A as well as patulin.
Ochratoxin A and citrinin developed in 11 kg parcels of amber durum wheat at 15% and 19% initial moisture content (MC) exposed to simulated bulk storage in a Manitoba granary for 60 weeks between July 1984 and September 1985. Other biotic and abiotic variables were monitored throughout the storage period. Ochratoxin A reached maximum levels of 11.8 and 0.11 ppm at 19 and 15% initial MC, respectively, during weeks 44-48; citrinin reached levels of 80.0 and 0.65 ppm at these respective moistures during the same period. The effect of 19% initial MC was significantly greater for the following variables: ochratoxin A, citrinin, Aspergillus flavus, Aspergillus glaucus group species, Alternaria species, Aspergillus versicolor, bacteria, fungal propagule count, seed germination, O2, CO2, moisture content, and fat acidity. Principal component analysis indicated that the first two components, describing greater than 60% of the variability in the data, partially defined the ecological relationships leading to mycotoxin production in the stored durum wheat system.
OBJECTIVES: Some strains of Chinese red yeast rice, when prepared by solid fermentation, produce compounds called monacolins that inhibit cholesterol production. When used as a dietary supplement to achieve and maintain healthy cholesterol levels, Chinese red yeast rice has significant potential to reduce health care costs and contribute to public health by reducing heart disease risk in individuals with moderate elevations of circulating cholesterol levels. Whereas one proprietary strain of Chinese red yeast rice has been demonstrated to lower cholesterol levels significantly in clinical trials, other strains being sold as Chinese red yeast rice dietary supplements have not undergone similar evaluation. In order to determine whether the results of a clinical trial conducted with one strain of Chinese red yeast rice could be generalized to other preparations of Chinese red yeast rice, nine different commercially available dietary supplements were purchased tested for chemical constituents. DESIGN: Monacolins were measured by high performance liquid chromatography (HPLC) that separates the various monacolins in Chinese red yeast rice. Citrinin concentration, a toxic fermentation byproduct, was measured by radioimmunoassay. RESULTS: Total monacolin content varied from 0% to 0.58% w/w and only 1 of 9 preparations had the full complement of 10 monacolin compounds. Citrinin was found at measurable concentrations in 7 of the 9 preparations. CONCLUSIONS: The findings from clinical trials demonstrating significant and clinically relevant cholesterol reduction using a defined Chinese red yeast rice preparation containing 10 different monacolins cannot be generalized to preparations that do not contain the same levels and profile of monacolins. Standardized manufacturing practices should be established for Chinese red yeast rice sold as a dietary supplement in order ensure equivalence of content of active ingredients in preparations being sold to the public and to limit the production of unwanted byproducts of fermentation such as citrinin. In common with other botanical dietary supplements, the full potential of this product will not be realized until standards for production and labeling of Chinese red yeast rice are further developed.
The etiology of Balkan endemic nephropathy and urinary tract tumours in the rural population of the endemic regions remains unknown. As one hypothesis involves mycotoxins, a survey was carried out to investigate the possible involvement of the nephrotoxic mycotoxins ochratoxin A and citrinin. Recently, this survey was extended to screening for the presence of other mycotoxins--aflatoxins, citrinin, sterigmatocystin and zearalenone. A total of 524 samples of home-produced and home-stored beans and maize from the harvests of 1984, 1985, 1986, 1989 and 1990 were analysed. Ochratoxin A was found in samples from both endemic and nonendemic areas, but more of the samples from affected families were contaminated, and at higher levels, than those from unaffected households. Citrinin and aflatoxins B1 and G1 were also found more frequently in samples from endemic areas. These results support the theory that mycotoxins are involved in the etiology of Balkan endemic nephropathy and urinary tract tumours.
Analytical methods are presented for detecting simultaneously 11 fungal metabolites (aflatoxins B1, B2, G1 and G2, citrinin, cyclopiazonic acid, mycophenolic acid, ochratoxin A, penicillic acid, penitrem A and roquefortine C) on different matrices. The methods were applied to determine the mycotoxins produced by different Penicillium crustosum, Penicillium nordicum and Penicillium verrucosum strains on yeast extract sucrose (YES) agar and cheese and bread analogues and are based on high-performance liquid chromatography (HPLC) and photodiode array detection (PDA). The growth substrate had a distinctive effect on the mycotoxin production ability of the fungi examined. The P. crustosum strains produced roquefortine C on all the substrates, with the highest amounts being detected on the cheese analogue. Penitrem A was synthesised on the cheese analogue only. The strains of P. verrucosum produced exclusively citrinin on YES, but both ochratoxin A and citrinin were detected in considerable amounts on the bread analogue. On the bread, toxin profiles varied significantly between the individual P. verrucosum strains. The cheese analogue was not favourable for the mycotoxin production of this species. The growth substrate had the least effect on the toxin production of the P. nordicum strains, which synthesised ochratoxin A in moderate amounts on all three media.