Detoxication of Citrinin with Kojic Acid by the Formation of the Citrinin-Kojic Acid Adduct, and the Enhancement of Kojic Acid Production by Citrinin via Oxidative Stress in Aspergillus parasiticus.

Our previous work showed that citrinin (CTN) produced bay inhibited the production of aflatoxin by We also reported that CTN was non-enzymatically converted to a novel CTN-KA adduct with kojic acid (KA) in aqueous condition. We herein observed that unlike CTN, the CTN-KA adduct does not show antimicrobial activity against or or any cytotoxic effect on HeLa cells, suggesting that CTN was detoxified by KA by the formation of the CTN-KA adduct. To examine the function of KA production by fungi, we isolated mutants with impaired KA production.

Deoxynivalenol and Nivalenol Toxicities in Cultured Cells: a Review of Comparative Studies.

The studies of the toxicities of trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) including cell proliferation, cytokine secretion, and the involvement of heat shock protein 90 (Hsp90) in their toxicities were reviewed. Trichothecene mycotoxins are extremely toxic to leukocytes and leukopenia is one of the leading signs of trichothecene toxicosis, implying that trichothecenes hinder cell proliferation. Both toxins retarded proliferation of all four cell lines tested.

Rubratoxin-B-induced secretion of chemokine ligands of cysteine-cysteine motif chemokine receptor 5 (CCR5) and its dependence on heat shock protein 90 in HL60 cells.

To elucidate the mechanism underlying rubratoxin B toxicity, the effects of rubratoxin B on the secretion of CCR5 chemokines, CCL3, CCL4, and CCL5, in a human promyelocytic leukemia cell line, HL60, were investigated. In addition, to examine whether the molecular chaperone 90-kDa heat shock protein (Hsp90) contributes to rubratoxin B toxicity, the effects of Hsp90-specific inhibitors, radicicol and geldanamycin, were investigated. Exposure to rubratoxin B for 24h induced secretion of each CCR5 chemokine, although the effect on CCL5 secretion was modest, and it enhanced secretion of proinflammatory cytokines tumor necrosis factor-α, CXCL8, and CCL2.

Detection of N-(1-deoxy-D-fructos-1-yl) Fumonisins B₂ and B₃ in Corn by High-Resolution LC-Orbitrap MS.

The existence of glucose conjugates of fumonisin B₂ (FB₂) and fumonisin B₃ (FB₃) in corn powder was confirmed for the first time. These "bound-fumonisins" (FB₂ and FB₃ bound to glucose) were identified as N-(1-deoxy-D-fructos-1-yl) fumonisin B₂ (NDfrc-FB₂) and N-(1-deoxy-D-fructos-1-yl) fumonisin B₃ (NDfrc-FB₃) respectively, based on the accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) analysis. Treatment on NDfrc-FB₂ and NDfrc-FB₃ with the o-phthalaldehyde (OPA) reagent also supported that D-glucose binding to FB₂ and FB₃ molecules occurred to their primary amine residues.

Detection of type A trichothecene di-glucosides produced in corn by high-resolution liquid chromatography-Orbitrap mass spectrometry.

The existence of di-glucosylated derivative of T-2 toxin in plant (corn powder) was confirmed for the first time in addition to that of HT-2 toxin. These masked mycotoxins (mycotoxin glucosides) were identified as T-2 toxin-di-glucoside (T2GlcGlc) and HT-2 toxin-di-glucoside (HT2GlcGlc) based on accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometric (LC-Orbitrap MS) analysis. Although the absolute structure of T2GlcGlc was not clarified, two glucose molecules were suggested to be conjugated at 3-OH position in tandem when considering the structure of T-2 toxin.

Opposite effects of two trichothecene mycotoxins, deoxynivalenol and nivalenol, on the levels of macrophage inflammatory protein (MIP)-1α and MIP-1β in HL60 cells.

To elucidate the mechanisms underlying the toxicities of the trichothecene mycotoxins deoxynivalenol and nivalenol, their effects on the secretion of anti-hematopoietic chemokines, macrophage inflammatory protein-1α (MIP-1α) and MIP-1β in human promyelocytic leukemia cell line HL60 were investigated. Exposure to deoxynivalenol for 24h significantly induced the secretion of chemokines. The induction of these chemokines may account for the leukopenia after exposure to trichothecene mycotoxins.

Rubratoxin B induces signs of fatty acid oxidation disorders (FAODs) in mice.

Rubratoxin B is a mycotoxin that causes hypoglycemia and fatty liver. We investigated the effect of rubratoxin B on hepatic glycogen content and regulation, because blood glucose levels are associated with hepatic glycogen storage. Mice were treated with 1.

Nuclear factor-κB inhibitors alleviate nivalenol-induced cytotoxicity in HL60 cells.

Tricothecene mycotoxins, such as nivalenol, are toxic to leukocytes. To elucidate the molecular mechanism of nivalenol toxicity, we investigated the involvement of nuclear factor-κB (NF-κB) in nivalenol-induced cytotoxicity in HL60 cells using the NF-κB inhibitors pyrrolidinedithiocarbamate (PDTC) and dexamethasone. Cells were treated with the chemicals for 24h before assays were performed.

Distinct distribution of deoxynivalenol, nivalenol, and ergosterol in Fusarium-infected Japanese soft red winter wheat milling fractions.

The occurrence of mycotoxins in small grain cereals and their retention in final products are serious concerns for food safety. Previously, we investigated the fate of deoxynivalenol and nivalenol in a Japanese soft red winter wheat cultivar during milling and we found that deoxynivalenol and/or nivalenol was readily distributed among flours for human consumption. In the present study, we analyzed the ergosterol concentrations in the milling fractions as an index of fungal biomass to elucidate the relationship between deoxynivalenol/nivalenol accumulation and fungal invasion into the grain, after the in-house validation of an analytical method for quantifying ergosterol in the resulting milling fractions (patent flour, low-grade flour, bran, and shorts).

Distribution of deoxynivalenol and nivalenol in milling fractions from fusarium-infected Japanese wheat cultivars.

The fate of the Fusarium mycotoxins deoxynivalenol and nivalenol during the milling of Japanese wheat cultivars artificially infected with Fusarium was investigated. Grain samples with different mycotoxin concentrations were milled using a laboratory-scale test mill to produce eight fractions: three breaking flours (1B, 2B, and 3B), three reduction flours (1M, 2M, and 3M), wheat bran, and wheat shorts. Patent flour for human consumption was made from the 1B, 2B, 1M, and 2M flours, and low-grade flour was made from 3B and 3M flours.

Limited surveillance of fumonisins in brown rice and wheat harvested in Japan.

Fumonisins are mycotoxins mainly produced by Fusarium verticillioides, which is a major contaminant of corn. However, there are sporadic reports of fumonisin contamination in wheat worldwide. The rice adherent fungus Gibberella fujikuroi is taxonomically closely related to F.

Rubratoxin B induces interleukin-6 secretion in mouse white adipose tissues and 3T3-L1 adipocytes.

Rubratoxin B is a mycotoxin that causes hepatic fatty changes. We examined whether white adipose tissue (WAT) contributes to rubratoxin B toxicity through effects on interleukin (IL)-6. Rubratoxin B was intraperitoneally injected into mice at 1.

Induced secretion of insulin-like growth factor binding protein-1 (IGFBP-1) in human hepatoma cell HepG2 by rubratoxin B.

The induction of insulin-like growth factor binding protein-1 (IGFBP-1) secretion by rubratoxin B was investigated using human hepatoma cell line HepG2; we also documented the involvement of stress-activated MAP kinases [c-Jun-N-terminal kinases (JNKs) and p38s] in this process. Rubratoxin B dramatically enhanced IGFBP-1 secretion, which peaked at a concentration of 40 microg/ml. The amount of IGFBP-1 mRNA increased with time and plateaued at 6 h.

Stress-activated MAP kinases regulate rubratoxin B-caused cytotoxicity and cytokine secretion in hepatocyte-derived HepG2 cells.

The effects of stress-activated MAP kinases (SAPKs) on biological phenomena in HepG2 cells caused by the hepatotoxin rubratoxin B were investigated. The amounts of phosphorylated (active) SAPKs (c-Jun N-terminal kinases (JNKs) and p38s) were significantly increased after treating cells with rubratoxin B, suggesting that rubratoxin B exerts its toxicity through SAPK signal transduction pathways. Compared with rubratoxin B-treatment alone, treatment with both rubratoxin B and the JNK inhibitor SP600125 decreased cell morphology changes and the activity of the apoptosis-related enzymes caspase-3 and caspase-7, indicating that JNKs are involved in rubratoxin B-induced apoptosis.

Rubratoxin B induced the secretion of hepatic injury-related colony stimulating factors in human hepatoma cells.

The induction of cytokine secretion by rubratoxin B was investigated using human hepatoma cell lines HepG2 and HuH-7. Interleukin (IL)-8, macrophage colony stimulating factor (M-CSF) and granulocyte-macrophage (GM)-CSF were detected in the media of rubratoxin B-treated both cell lines, and their levels peaked at about 40 microg/ml. Rubratoxin B-induced cytokine secretion was enhanced by tumor necrosis factor (TNF)-alpha in HepG2 cells.

Enhancing effect of zinc on hepatoprotectivity of epigallocatechin gallate in isolated rat hepatocytes.

The influence of metal ions (Fe2+, Cu2+, Zn2+) on the hepatoprotective activity of epigallocatechin gallate (EGCG) against hepatotoxin-induced cell injury was investigated. Primary cultures of rat hepatocytes were treated with a well-known hepatotoxin, bromobenzene (BB), in the presence of EGCG only or EGCG plus each metal ion. After 24 h, 0.

Suppression of cytotoxin-induced cell death in isolated hepatocytes by tea catechins.

To elucidate the hepatoprotective effects of green tea catechins, the following experiments were conducted utilizing (-)-epigallocatechin-3-gallate (EGCG), the major component of green tea catechin, together with other catechins. The protective effects of catechins against hepatotoxins, bromobenzene or rubratoxin B, were examined in primary cultures of rat hepatocytes. Bromobenzene and rubratoxin B are known to induce necrosis and apoptosis of cells, respectively.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced down-regulation of glucose transporting activities in mouse 3T3-L1 preadipocyte.

The possibility that 3T3-L1 preadipocytes, while the level of its glucose uptake activity is relatively low, may offer a useful tool for studying the cause for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced "lipolytic response" was studied. It was established first, that TCDD causes reduction of glucose uptake, one of the hallmark events of the lipolytic process. Then the function of c-Src was investigated.

Effects of src-deficiency on the expression of in vivo toxicity of TCDD in a strain of c-src knockout mice procured through six generations of backcrossings to C57BL/6 mice.

The effect of TCDD was studied in c-src-deficient C57BL6-src(tm1sor) (N6 src -/- and -/+) mice, and their wild-type littermate mice (N6 src +/+). The former was created from the original strain of B6, 129-src(tm1sor) mice through six generations of backcrossings with C57BL6 mice. The results of a high dose TCDD toxicity tests in male mice indicated that N6 src-/+ mice were significantly less responsive to the toxic action of TCDD (115 microg/kg single i.