naphthoquinones and xanthomegnin

Mycotoxin problems are one of great concern to health scientists. Toxic fungal metabolites such as aflatoxins, trichothecenes, zearalenone and others are contaminated in our environments and induce various diseases. In this manuscript, the author will summarize the recent advances on toxicology of mycotoxins in special references to toxicological characters, cytotoxicity, genotoxicity (mutagenicity and carcinogenicity), metabolism, and biochemical mode of action. Interaction of mycotoxins with cellular components will be reviewed in order to clarify the toxicological characteristics of mycotoxins such as aflatoxins, trichothecenes, zearalenone, toxic peptides, and anthraquinoid mycotoxins.

Topics: Adenosine Triphosphatases; Aflatoxin B1; Aflatoxins; Animals; Aurovertins; Biotransformation; Carcinogens; Chemical Phenomena; Chemistry; Cyclobutanes; Cytochalasins; Electron Transport; Energy Metabolism; Gene Expression Regulation; Griseofulvin; Humans; Immunosuppressive Agents; Mutagens; Mycotoxins; Naphthoquinones; Ochratoxins; Peptides, Cyclic; Protein Biosynthesis; Trichothecenes; Xanthenes; Xanthones; Zearalenone

It is thought that fungi protect themselves from predation by the production of compounds that are toxic to soil-dwelling animals. Here, we show that a nontoxic pigment, the bis-naphthopyrone aurofusarin, protects Fusarium fungi from a wide range of animal predators. We find that springtails (primitive hexapods), woodlice (crustaceans), and mealworms (insects) prefer feeding on fungi with disrupted aurofusarin synthesis, and mealworms and springtails are repelled by wheat flour amended with the fungal bis-naphthopyrones aurofusarin, viomellein, or xanthomegnin. Predation stimulates aurofusarin synthesis in several Fusarium species and viomellein synthesis in Aspergillus ochraceus. Aurofusarin displays low toxicity in mealworms, springtails, isopods, Drosophila, and insect cells, contradicting the common view that fungal defence metabolites are toxic. Our results indicate that bis-naphthopyrones are defence compounds that protect filamentous ascomycetes from predators through a mechanism that does not involve toxicity.

Topics: Adaptation, Physiological; Animals; Arthropods; Aspergillus ochraceus; Food Preferences; Fusarium; Naphthoquinones; Pigments, Biological; Predatory Behavior

Trichophyton rubrum is a human pathogenic fungus. As a dermatophyte it causes athlete's foot, fungal infection of nails, jock itch and ringworm. The pigmentation of T. rubrum is variable and can range from white or yellow to wine-red. We demonstrate that the pigmentation is strongly influenced by pH. Under alkaline conditions, T. rubrum has a red pigmentation, whereas at acid conditions, T. rubrum has a yellow pigmentation. Moreover, the color change immediately from yellow to red by adding NaOH and reverse immediately from red to yellow by adding HCl. We suggest that the chemical compound Xanthomegnin is responsible for red as well for yellow pigmentation in T. rubrum. To figure out, why T. rubrum has red pigmentation on Trichophyton medium, adjust to alkaline, but not on Synthetic-Complete medium, also adjusted to alkaline, we measure the pH of liquid media, adjusted to pH 3.5, 6 and 8, over a period of four weeks. The pH of both cultivation media changes significantly, with a maximum of five pH levels. Whereas the Trichophyton medium, initially adjusted to pH 8, stays alkaline, the pH of the Synthetic-Complete medium drops to acid conditions. The acidification of the SC medium and the alkalization of the Trichophyton medium explains the different pigment color of the T. rubrum colonies.

Topics: Culture Media; Humans; Hydrogen-Ion Concentration; Naphthoquinones; Pigmentation; Pigments, Biological; Trichophyton

In the course of a search for anti-dormant mycobacterial substances from marine-derived microorganisms, viomellein (1) and xanthomegnin (2) were re- discovered from the active fraction of the culture of a marine-derived Aspergillus sp. together with rubrosulphin (3) and asteltoxin (4) on the guidance of bioassay-guided separation. In particular, compound 1 showed higher activity against the dormant than against actively growing Mycobacterium bovis BCG and weak activity against M smegmatis. Furthermore, evidence that compound 1 did not directly bind to plasmid DNA suggests its anti-mycobacterial activity differs from its direct chelating effect on the mycobacterial genome.

Topics: Antitubercular Agents; Aspergillus; Dimerization; Microbial Sensitivity Tests; Mycobacterium; Naphthoquinones; Seawater

Mycotoxins are putative virulence factors of fungi that play an important role in the pathogenesis of fungal infections. Mycotoxin production has been used as a diagnostic marker for the early diagnosis of fungal diseases. Using high-performance liquid chromatography, we investigated whether the fungal strains recovered from eye tissue samples obtained from patients with ocular mycoses produced the mycotoxin xanthomegnin. We tested 62 well-characterized strains of fungi, including Aspergillus spp. (n = 14), Exophiala spp. (n = 9), Fusarium spp. (n = 15), and several molds (n = 24). All isolates were identified to the species level using PCR and DNA sequencing of rRNA genes. We detected xanthomegnin activity (0.02 µg/ml) in one of the three Aspergillus flavus strains. However, we were unable to detect xanthomegnin in any of the other 61 fungal strains. Our result suggests that xanthomegnin production was infrequent in fungal strains recovered from patients with ocular mycoses.

Topics: Aspergillus; Exophiala; Eye Infections, Fungal; Fusarium; Humans; Mycoses; Mycotoxins; Naphthoquinones

Here, we aimed to discriminate the Trichophyton rubrum and Trichophyton mentagrophytes complexes, via detection of xanthomegnin using HPLC. We concluded that it is not a reliable technique for discriminating the two complexes, because strains belonging to both T. rubrum and T. mentagrophytes complexes displayed xanthomegnin activity.

Topics: Chromatography, High Pressure Liquid; Naphthoquinones; Trichophyton

Xanthomegnin, a mutagenic mycotoxin best known as an agent of nephropathy and death in farm animals exposed to food-borne Penicillium and Aspergillus fungi, was first isolated about 35 y ago as a diffusing pigment from cultures of the dermatophyte, Trichophyton megninii. This study investigates the production of xanthomegnin by the most common dermatophytic species, Trichophyton rubrum, both in dermatologic nail specimens and in culture. In view of the labile nature of xanthomegnin, a chromatographic procedure was developed to allow high-performance liquid chromatography analysis within 1 h of sample extraction. In cultures, Tricho- phyton rubrum produced xanthomegnin as a major pigment that appears to give the culture its characteristic red colony reverse. Xanthomegnin was also repeatedly extracted from human nail and skin material infected by Trichophyton rubrum. The level of xanthomegnin present, however, varied among the clinical samples studied. Xanthomegnin was not detected in uninfected nails. These results show that patients with Trichophyton rubrum infections may be exposed to xanthomegnin, although the consequences of such an exposure are not currently known.

Topics: Chromatography, High Pressure Liquid; Humans; Nails; Naphthoquinones; Skin; Tinea; Trichophyton

Penicillium freii (Lund and Frisvad 1994) mutants deficient in the synthesis of xanthomegnin were isolated. In vitro translated mRNA populations from selected radiation induced mutants and naturally occurring P. freii strains not able to produce xanthomegnin were examined by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Specific translation products were absent in mutants and natural isolates unable to produce xanthomegnin metabolites. One mutant (TSM 73) did not produce several of these translation products, indicating that a mutation in a regulatory gene involved in xanthomegnin production had occurred.

Topics: Electrophoresis, Gel, Two-Dimensional; Fungal Proteins; Gene Expression Regulation, Fungal; Genetic Variation; Hydroxyquinolines; Mutagenesis; Naphthoquinones; Penicillium; Protein Biosynthesis; RNA, Messenger; Xanthine; Xanthines

Wheat seed was adjusted to 18, 20, 22, 24 and 26% moisture content (m.c.), and stored for 240 days at 4 or 10 degrees C following inoculation with a strain of Penicillium viridicatum producing the toxins, xanthomegnin (XA), viomellein (VIO), and brevianamide A (BA). Wheat kernels were not sterilized before inoculation. The concentration of ergosterol (ERG), a chemical indicator of fungal biomass, remained constant at 18% m.c./4 degrees C, but increased under the other conditions. The time before a detectable increase of ERG concentration was higher and the rate of ERG production lower with decreasing moisture content and temperature. XA and BA were produced at both temperatures at 20-26% m.c., VIO was produced at 22-26% m.c./4 degrees C and 20-26% m.c./10 degrees C. The results suggest or indicate that the onset of XA, VIO and BA production (detection limits: 10, 15, and 0.1 micrograms/kg, respectively) coincided with the onset of ERG production. Maximum toxin contents were lower with decreasing moisture content at both temperatures, but were similar at 4 and 10 degrees C at 22-26% m.c. It is concluded that wheat contaminated with P. viridicatum should not be stored beyond the onset of ergosterol production; maximum storage periods are recommended.

Topics: Alkaloids; Cold Temperature; Ergosterol; Food Microbiology; Food Preservation; Mycotoxins; Naphthoquinones; Penicillium; Pigments, Biological; Piperazines; Refrigeration; Seeds; Spiro Compounds; Triticum

The myotoxins xanthomegnin and viridicatumtoxin were not teratogenic when administered orally to pregnant ICR mice during the 8-12th and 8-13th days of gestation, respectively. Viridicatumtoxin produced high mortality in mice given 200, 250 or 350 mg/kg of body weight.

Topics: Animals; Dose-Response Relationship, Drug; Female; Mice; Mice, Inbred ICR; Mycotoxins; Naphthoquinones; Pregnancy; Pregnancy, Animal; Teratogens

The genotoxicity and mutagenicity of several kinds of quinone pigments from pathogenic fungi were examined by means of the hepatocyte primary culture (HPC)/DNA repair test and of Ames test with TA98 and TA100. Clear genotoxicity of the two quinone chemicals, xanthomegnin and luteosporin were observed in the HPC/DNA repair test, though definite mutagenicity was not detected in the Salmonella microsome test. These two pigments are thus suspected to be genotoxic carcinogens.

Topics: Animals; Dimethyl Sulfoxide; DNA Repair; Mutagenicity Tests; Mycotoxins; Naphthoquinones; Pigments, Biological; Rats

A high pressure liquid chromatographic (HPLC) method is described for the determination of xanthomegnin in grains and mixed animal feeds at levels ranging from 150 to 1200 ng/g. This is equivalent to actual amounts of xanthomegnin injected on the HPLC system at from 15 to 120 ng/injection. Xanthomegnin is extracted with chloroform and 0.1M phosphoric acid. An aliquot of the crude extract is purified by column chromatography using a commercially available silica gel cartridge. Xanthomegnin is then separated from the remaining interferences by HPLC with a reverse phase C-8 column, and subsequently determined by absorbance detection at 405 nm. Elapsed time for the method from initial extraction to final HPLC determination is approximately 1 h. Recoveries of xanthomegnin added to grains and animal feeds at levels from 150 to 1200 ng/g averaged 82% with a coefficient of variation of 10.2%.

Topics: Animal Feed; Animals; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Edible Grain; Naphthoquinones

A medium, pentachloronitrobenzene-rose bengal-yeast extract-sucrose agar (PRYES), for the isolation of moulds occurring during storage of cereals has been developed and compared with other selective media. The basal medium is yeast extract agar containing 15% sucrose (w/v). In addition to the sucrose content further selective measures include the addition of antibacterial antibiotics chloramphenicol and chlortetracycline (50 mg/l), the fungicides rose bengal (25 mg/l each), and pentachloronitrobenzene (1 g/l) and a low incubation temperature (20 degrees C). Members of the Mucorales were completely inhibited, and fast-growing species of other moulds were slightly inhibited, allowing important storage moulds to develop. The important ochratoxin A and citrinin-producing Penicillium viridicatum group II was indicated by a typical violet brown reverse on PRYES. Producers of xanthomegnin and viomellein (P. viridicatum group I and P. aurantiogriseum) were indicated on PRYES by their yellow reverse and obverse colours. The medium was used for screening 40 samples of barley, and moulds with the characteristic colours were all identified as the species mentioned above.

Topics: Citrinin; Culture Media; Edible Grain; Food Microbiology; Hordeum; Mycotoxins; Naphthoquinones; Ochratoxins; Penicillium; Triticum

A method was developed for the production and purification of xanthomegnin from Penicillium viridicatum (NRRL 6430) cultured on rice at 15 degrees C for 29 days. Liquid-liquid extraction followed by high-pressure liquid chromatography afforded 440 mg of crystalline xanthomegnin per kg of rice.

Topics: Chromatography, High Pressure Liquid; Mycotoxins; Naphthoquinones; Penicillium

The interaction of bovine serum albumin (BSA) and xanthomegnin, an uncoupler of oxidative phosphorylation was studied spectrophotometrically. BSA caused a marked red shift of the absorption maxima of xanthomegnin from 406 to 555 nm but heating the reaction mixture abolished the BSA-induced spectral change. Spectrophotometric titrations of xanthomegnin with increasing concentrations of BSA gave a molar ratio of unity for these two components with an association constant of 1.4 X 10(6) M-1. The absorption spectrum of xanthomegain was affected by pH changes of the system. The pK was found to be 8.4 and was significantly shifted to a lower pH (pH 5.4) in the presence of BSA. The BSA-induced spectral change was abolished by sodium dodecyl-sulfate or 1 anilino-8 napthalene sulfonic acid but not by L-tryptophan. These results would suggest that the characteristic spectral changes of xanthomeginin are caused by reversible binding to a strong, hydrophobic anion binding site of BSA. In many respects the binding resembles that of bilirubin with this same protein. In the latter reaction, the red shift was much smaller than the reaction of BSA and xanthomegnin.

Topics: Anilino Naphthalenesulfonates; Hydrogen-Ion Concentration; Mycotoxins; Naphthoquinones; Protein Binding; Serum Albumin, Bovine; Sodium Dodecyl Sulfate; Spectrophotometry; Tryptophan

Effects of xanthomegnin and duclauxin on mitochondrial respiration, L1210 culture cells of murine leukemia and Ehrlich ascitic tumor were compared. Both compounds exhibited similarly potent uncoupling effects on the oxidative phosphorylation of mitochondria and cyto-toxicities on the culture cells, but they were not equal in the anti-tumor activity on Ehrlich ascitic tumor. Duclauxin markedly increased the life-span of mice which were i.p. inoculated with Ehrlich ascitic tumor but xanthomegnin did not exhibit such effect as duclauxin.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Cells, Cultured; Chromones; Female; Leukemia, Experimental; Mice; Mice, Inbred ICR; Mitochondria; Naphthoquinones; Oxidative Phosphorylation; Rats; Uncoupling Agents

The interaction of xanthomegnin, a quinone pigment, with the mitochondrial respiratory chain was demonstrated. Xanthomegnin was reduced by succinate, in the presence of submitochondrial particles or mitochondria, only after all oxygen had been consumed in the system, and the reduction was inhibited by antimycin A or KCN. Xanthomegnin was immediately reduced by NADH in a similar system, the reduced xanthomegnin was reoxidized by oxygen but the reduction by NADH was not inhibited by antimycin A or KCN. Xanthomegnin was also immediately reduced by NADH catalyzed by a purified particulate NADH dehydrogenase complex showing a molar ratio of 2 moles NADH for one mole of xanthomegnin. Reoxidation of the reduced pigment by oxygen occurred in this system. Oxygen consumption was accelerated when xanthomegnin was added to a reaction medium containing NADH, NADH segment and cytochrome c oxidase. Subsequent addition of cytochrome c resulted in a further marked acceleration of oxygen consumption. These results suggest that xanthomegnin interacts with the NAD-linked respiratory chain to produce a xanthomegnin shunt, but this does not occur with the succinate-linked chain.

Topics: Animals; Chemical Phenomena; Chemistry; Electron Transport; In Vitro Techniques; Mitochondria; Naphthoquinones; Oxidation-Reduction; Pigments, Biological

Topics: Animals; Cytochrome c Group; Electron Transport; Microsporum; Mitochondria, Liver; NAD; Naphthoquinones; Oxidation-Reduction; Pigments, Biological; Rats; Uncoupling Agents

A method is described for the detection and quantitative analysis of xanthomegnin in corn samples. Initial extraction with CHCl3 in the presence of 0.5M H3PO4 is followed by additional purification using silica gel column chromatography. A high pressure liquid chromatograph equipped with a microparticle silica gel column and a 405 nm absorbance detector is used for detection and quantitation of the xanthomegnin. The identity of xanthomegnin is confirmed by thin layer chromatography on silica gel plates developed with benzene-methanol-acetic acid (90 + 5 + 5). The recovery of xanthomegnin added to corn samples at levels of 0.75--9.6 mg/kg averaged 41% with a coefficient of variation of 25%.

Topics: Chromatography, High Pressure Liquid; Mycotoxins; Naphthoquinones; Zea mays

Fungal isolates from legumes were cultured on rice and examined for production of the toxic mold metabolites xanthomegnin and viomellein. Six of 14 Aspergillus ochraceus isolates produced from 0.3 to 1.3 mg of xanthomegnin per g and 0.1 to 1.0 mg of viomellein per g. One of nine isolates of Penicillium cyclopium produced 0.1 mg of xanthomegnin per g and 0.06 mg of viomellein per g. Three of nine P. viridicatum isolates produced from 0.4 to 1.6 mg of xanthomegnin per g and 0.2 to 0.4 mg of viomellein per g. This is the first report of xanthomegnin and viomellein production by A. ochraeus and P. cyclopium.

Topics: Aspergillus; Culture Media; Fabaceae; Food Microbiology; Mycotoxins; Naphthoquinones; Oryza; Penicillium; Plants, Medicinal; Species Specificity

By using thin-layer chromatography and infrared spectroscopy, xanthomegnin and viomellein have been isolated and identified from species of the Aspergillus ochraceus group. A correlation was established between the occurrence of these fungal quinones in the fungal cultural products and the ability of these products to induce mycotoxicosis in mice. In addition, a method was employed to estimate the amount of xanthomegnin and viomellein produced by the fungi.

Topics: Animals; Aspergillus; Chromatography, Thin Layer; Female; Male; Mice; Mycotoxins; Naphthoquinones; Species Specificity; Spectrophotometry, Infrared

Topics: Animals; Biotransformation; Chemical and Drug Induced Liver Injury; Diet; Kidney; Liver; Male; Mice; Mycotoxins; Naphthoquinones; Penicillium; Pigments, Biological

Topics: Biological Products; Humans; Naphthoquinones; Pigments, Biological; Trichophytin; Trichophyton