Effect of probiotic containing Saccharomyces boulardii on experimental ochratoxicosis in broilers: hematobiochemical studies.
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In the present investigation, the toxicopathological effects of ochratoxin A of 0.5 ppm on hematobiochemical parameters of broilers were studied with efficacy of dietary concentration of probiotic containing yeast culture Saccharomyces boulardii of 10 mg/kg of feed. One hundred twenty day old chicks were randomly divided into four groups, thirty chicks each. Groups A and C chicks were offered normal feed and that added with probiotic Saccharomyces boulardii respectively. The birds in group B were fed ochratoxin A of 0.5 ppm of feed. Where as, the birds of group D, were fed with ochratoxin A of 0.5 ppm along with probiotic Saccharomyces boulardii of 10 mg/kg of diet. Hematological studies carried revealed significant decrease in the haemoglobin and packed cell volume in birds of group B and reduced effect in birds of group D due to probiotic. Biochemical profiles revealed significant improvement in probiotic treated group D when compared with decreased values of Total protein, albumin, globulin and increased levels of serum creatinine and SGPT in birds of groups B. (+info)
Proximal tubular toxicity of ochratoxin A is amplified by simultaneous inhibition of the extracellular signal-regulated kinases 1/2.
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Ochratoxin A (OTA) is a mycotoxin involved in the development of chronic nephropathies and a known carcinogen. As we have shown previously, OTA activates mitogen-activated protein kinases [extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-jun amino-terminal kinase (JNK), and extracellular-regulated protein kinase 38 (p38)] in proximal tubular cells (opossum kidney and normal rat kidney epithelial). ERK1/2, JNK, or p38 are thought to mediate opposite action on apoptosis, fibrosis, and inflammation. As we have already shown, OTA activates the latter processes. Here, we investigated the effect of OTA in the absence or presence of the ERK1/2 inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4bis(2-aminophenylthio)-butadiene] to test whether OTA then will exert increased toxicity. In the presence of ERK1/2 inhibition, OTA decreased cell number and protein to a significantly larger extent compared with OTA alone. The same was true for epithelial tightness, apoptosis (caspase-3 activity), and necrosis (lactate dehydrogenase release). Furthermore, simultaneous inhibition of ERK1/2 amplified the effect of OTA on markers of inflammation (nuclear factor of the kappa-enhancer in B cells activity), fibrosis (collagen secretion), and epithelial mesenchymal transition (alpha smooth muscle actin). OTA induces phenomena typical for chronic interstitial nephropathy and activates ERK1/2, JNK, and p38 in proximal tubular cells. Inhibition of ERK1/2 aggravates the effects of OTA or even induces toxicity at normally nontoxic concentrations. This is highly likely due to activation of JNK and p38. Our data indicate a new mechanistic explanation for the toxic actions induced by OTA, and they are notable with respect to a possible coexposition of the kidney to OTA and naturally occurring ERK1/2 inhibitors. Finally, our data give rise to an attractive hypothesis on the coincidence of increased OTA exposition and urinary tract tumors in humans. (+info)
Ochratoxin A in grain dust--estimated exposure and relations to agricultural practices in grain production.
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Ochratoxin A (OTA) is a nephrotoxin frequently contaminating grains. OTA inhalation during grain handling may therefore represent a health risk to farmers, and was the subject of this study. Airborne and settled grain dust was collected during grain work on 84 Norwegian farms. Climate and agricultural practices on each farm were registered. Penicillium spp., Aspergillus spp. and OTA in settled dust were measured. Settled dust contained median 4 microg OTA/kg dust (range 2-128), correlating with Penicillium spp. (median 40 cfu/mg; range 0-32000, rs =0.33; p < 0.01). Similar levels were found across grain species, districts and agricultural practices. Penicillium levels, but not OTA levels, were higher in storage than in threshing dust (p=0.003), and increased with storage time (rs =0.51, p < 0.001). Farmers were exposed to median 1 mg/m3 (range 0.2-15) dust during threshing and median 7 mg/m3 (range 1-110) dust during storage work, equalling median 3.7 pg/m3 (range 0.6-200) and median 40 pg/m3 (range 2-14000) OTA, respectively (p < 0.001). Agricultural practices could not predict OTA, Penicillium or Aspergillus contamination. Compared to oral intake of OTA, the inhalant exposure during grain work was low, although varying by more than 1,000-fold. However, the farmers may occasionally be highly exposed, particularly during handling of stored grain. (+info)
Ochratoxin a content of urine samples of healthy humans in Hungary.
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The ochratoxin A (OTA) content of urine samples from 88 healthy humans living at five settlements in three counties of Hungary was determined by immunoaffinity column cleanup and high-performance liquid chromatography (HPLC). OTA was detected in 61% of the samples in an average concentration of 0.013 ng/ml (range: 0.006-0.065 ng/ml). OTA concentrations measured in urine samples from men and women were not significantly different. The OTA concentration of samples from Heves county was significantly (t-test; p < 0.003) higher than that of samples from Hajdu-Bihar and Somogy counties. The regional differences in OTA concentration of urine samples indicate regional differences in the OTA exposure of the human population. Further studies are necessary to determine the cause of the regional differences in the OTA intake. The studies allow us to conclude that the OTA intake of the majority of the Hungarian population is low (< 1 ng/kg of body weight per day) but a certain part of the rural population may take up higher levels of OTA. (+info)
Study of Spanish grape mycobiota and ochratoxin A production by Isolates of Aspergillus tubingensis and other members of Aspergillus section Nigri.
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The native mycobiota of five grape varieties grown in Spain has been studied. Four (Bobal, Tempranillo, Garnacha, and Monastrell) were red varieties and one (Moscatel) was white. The main fungal genera isolated were Alternaria, Cladosporium, and Aspergillus. The isolation frequency of Aspergillus spp. section Nigri in contaminated samples was 82%. Ochratoxin A (OTA) production was assessed using yeast extract-sucrose broth supplemented with 5% bee pollen. Cultures of 205 isolates from this section showed that 74.2% of Aspergillus carbonarius and 14.3% of Aspergillus tubingensis isolates produced OTA at levels ranging from 1.2 to 3,530 ng/ml and from 46.4 to 111.5 ng/ml, respectively. No Aspergillus niger isolate had the ability to produce this toxin under the conditions assayed. Identification of the A. niger aggregate isolates was based on PCR amplification of 5.8S rRNA genes and its two intergenic spacers, internal transcribed spacer 1 (ITS1) and ITS2, followed by digestion with restriction endonuclease RsaI of the PCR products. The restriction patterns were compared with those from strains of A. niger CECT 2807 and A. tubingensis CECT 20393, held at the Spanish Collection of Type Cultures. DNA sequencing of the ITS1-5.8S rRNA gene-ITS2 region of the OTA-producing isolates of A. tubingensis matched 99 to 100% with the nucleotide sequence of strain A. tubingensis CBS 643.92. OTA determination was accomplished by liquid chromatography with fluorescence detection. OTA confirmation was carried out by liquid chromatography coupled to ion trap mass spectrometry. The results showed that there are significant differences with regard to the isolation frequency of ochratoxinogenic fungi in the different grape varieties. These differences were uncorrelated to berry color. The ability of A. tubingensis to produce OTA and the influence of grape variety on the occurrence of OTA-producing fungi in grapes are described in this report for the first time. (+info)
The impact of plasma protein binding on the renal transport of organic anions.
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Drugs and xenobiotics bind to plasma proteins with varying degrees of affinity, and the amount of binding has a direct effect on free drug concentration and subsequent pharmacokinetics. Multiple active and facilitative transport systems regulate the excretion of anionic compounds from the blood in excretory and barrier tissues. Assumptions are made about in vivo substrate affinity and route of elimination based on data from plasma protein-free in vitro assays, particularly following expression of cloned transporters. Ochratoxin A (OTA), a fungal mycotoxin, is a high-affinity substrate for several renal secretory organic anion transporters (OATs), and literature suggests that this elimination pathway is the route of entry leading to proximal tubule-targeted toxicity. However, OTA is known to bind to several plasma proteins with a high affinity, particularly serum albumin, which may impact elimination. In this study, we have systematically examined the handling of OTA and other organic anions, estrone sulfate (ES) and methotrexate (MTX), by OATs in the presence of serum albumin. Increasing concentrations of albumin markedly reduced uptake of OTA by both Xenopus laevis oocytes expressing OATs 1, 3, and 4 and organic anion-transporting polypeptide 1. For all transporters tested, virtually all mediated OTA uptake was eliminated by an albumin concentration equivalent to 10% of that present in the blood plasma. Thus, OTA uptake is dependent on the free substrate concentration and severely limited by binding to human serum albumin. MTX and ES uptake were likewise dependent on free concentration. (+info)
A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.
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Ochratoxin A (OTA) is a mycotoxin occurring naturally in a wide range of food commodities. In animals, it has been shown to cause a variety of adverse effects, nephrocarcinogenicity being the most prominent. Because of its high toxic potency and the continuous exposure of the human population, OTA has raised public health concerns. There is significant debate on how to use the rat carcinogenicity data to assess the potential risk to humans. In this context, the question of the mechanism of action of OTA appears of key importance and was studied through the application of a toxicogenomics approach. Male Fischer rats were fed OTA for up to 2 years. Renal tumors were discovered during the last 6 months of the study. The total tumor incidence reached 25% at the end of the study. Gene expression profile was analyzed in groups of animals taken in intervals from 7 days to 12 months. Tissue-specific responses were observed in kidney versus liver. For selected genes, microarray data were confirmed at both mRNA and protein levels. In kidney, several genes known as markers of kidney injury and cell regeneration were significantly modulated by OTA. The expression of genes known to be involved in DNA synthesis and repair, or genes induced as a result of DNA damage, was only marginally modulated. Very little or no effect was found amongst genes associated with apoptosis. Alterations of gene expression indicating effects on calcium homeostasis and a disruption of pathways regulated by the transcription factors hepatocyte nuclear factor 4 alpha (HNF4alpha) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were observed in the kidney but not in the liver. Previous data have suggested that a reduction in HNF4alpha may be associated with nephrocarcinogenicity. Many Nrf2-regulated genes are involved in chemical detoxication and antioxidant defense. The depletion of these genes is likely to impair the defense potential of the cells, resulting in chronic elevation of oxidative stress in the kidney. The inhibition of defense mechanism appears as a highly plausible new mechanism, which could contribute to OTA carcinogenicity. (+info)
Ochratoxin A production and amplified fragment length polymorphism analysis of Aspergillus carbonarius, Aspergillus tubingensis, and Aspergillus niger strains isolated from grapes in Italy.
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Ochratoxin A is a potent nephrotoxin and a possible human carcinogen that can contaminate various agricultural products, including grapes and wine. The capabilities of species other than Aspergillus carbonarius within Aspergillus section Nigri to produce ochratoxin A from grapes are uncertain, since strain identification is based primarily on morphological traits. We used amplified fragment length polymorphisms (AFLPs) and genomic DNA sequences (rRNA, calmodulin, and beta-tubulin genes) to identify 77 black aspergilli isolated from grape berries collected in a 2-year survey in 16 vineyards throughout Italy. Four main clusters were distinguished, and they shared an AFLP similarity of <25%. Twenty-two of 23 strains of A. carbonarius produced ochratoxin A (6 to 7,500 microg/liter), 5 of 20 strains of A. tubingensis produced ochratoxin A (4 to 130 microg/liter), 3 of 15 strains of A. niger produced ochratoxin A (250 to 360 microg/liter), and none of the 19 strains of Aspergillus "uniseriate" produced ochratoxin A above the level of detection (4 microg/liter). These findings indicate that A. tubingensis is able to produce ochratoxin and that, together with A. carbonarius and A. niger, it may be responsible for the ochratoxin contamination of wine in Italy. (+info)