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      The Kidneys of Infant Mice are not Sensitive to the Food Mycotoxin Contaminant Nivalenol

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          Abstract

          Nivalenol (NIV) is a trichothecene mycotoxin produced by Fusarium fungi that frequently contaminates agricultural commodities. Dietary administration of NIV to adult mice affects the renal glomeruli, but data about NIV toxicity in human infants are limited. To evaluate the effects of NIV on infant kidneys, 3-week-old male ICR-derived glomerulonephritis (ICGN) and ICR mice were administered 0, 4, 8 or 16 ppm NIV in diet for 4 weeks, and their renal status was compared with age-matched or adult ICR mice. In ICGN mice, the number of glomeruli showing mesangial expansion and α-smooth muscle actin (SMA)-positive mesangial cells was higher with 16 ppm NIV compared with controls. No other significant differences were observed in ICGN mice. In infant ICR mice, the IgA serum concentrations were significantly elevated without glomerular morphological changes in the 16 ppm NIV group. There was no difference in NIV sensitivity in the kidneys of infant ICGN and ICR mice. These data suggest that the kidneys in infant mice are not sensitive to nivalenol under the present conditions.

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          Most cited references23

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          Trichothecenes in the environment: relevance to human health.

          D Sudakin (2003)
          Trichothecenes are agriculturally important mycotoxins of relevance to human health. Fungi capable of producing trichothecenes can be found throughout the world, and include certain species of Fusarium, Myrothecium, and Stachybotrys. The production of mycotoxins by these toxigenic species is determined by genetic factors and the environmental conditions of their growth. The environmental fate of trichothecenes may be affected by other microorganisms that can detoxify them. Deoxynivalenol and T-2 toxin are examples of trichothecenes that are detectable as natural and unavoidable contaminants of certain agricultural commodities as well as commercial foods. Current estimates of dietary exposure to deoxynivalenol and T-2 toxin are below thresholds for adverse effects that have been reported in experimental animal studies, although historical epidemics of human illness have rarely been described in association with consumption of food derived from heavily contaminated grains. The toxicodynamic properties of trichothecenes include inhibition of protein synthesis and immunomodulatory effects. Very little information is available relating to their toxicokinetics and toxicodynamics in humans. While there is general agreement that the diet represents an important source of human exposure to trichothecenes, risk assessment from non-dietary routes of exposure is complicated by the limited epidemiological data that are currently available.
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            Adriamycin alters glomerular endothelium to induce proteinuria.

            The pathophysiology underlying the nephrotic syndrome is becoming clear for several inherited podocytopathies; the mechanisms of injury that lead to the acquired forms of this disease are not well understood. We explored these mechanisms using the mouse model of adriamycin-induced proteinuria.We estimated the fractional clearances for FITC-Ficolls, albumin, and neutral albumin in cooled, isolated,perfused kidneys (cIPK) in situ. Treatment with adriamycin led to a significant increase in the fractional clearance of albumin and of Ficoll with radii larger than 20 A. Neutral albumin (33.4 A) and similarly sized Ficoll behaved similarly to each other. In addition, adriamycin led to a significant loss of charge density and size selectivity of the glomerular barrier. The thickness of the glomerular endothelial surface layer(i.e., or the glycocalyx) in adriamycin-treated animals was only 20% of that in normal animals. Finally,several proteoglycans were downregulated in isolated glomeruli. In summary, adriamycin thins the glomerular glycocalyx, perhaps by downregulating proteoglycan synthesis, and alters glomerular charge- and size selectivity. These data suggest that the glomerular endothelium may play a role in the pathogenesis of proteinuric renal diseases.
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              Mycotoxins in rice.

              Mycotoxin contamination in rice is usually lower as in wheat or corn. However, there are some reports that rice has been contaminated with mycotoxins such as aflatoxin B1, B2, G1, G2 (AFS), citrinin, deoxynivalenol (DON), fumonisin B1, B2, B3 (FMS), fusarenon-X (Fus.-X), nivalenol (NIV), ochratoxin A (OTA), sterigmatocystin (STE), and zearalenone. Rice in Japan is preserved in warehouses where moisture content and temperature are regulated. Therefore, mycotoxin contamination from post harvest fungal growth occurs very seldom. Trichothecenes, aflatoxins, and STE in rice were recently analyzed in our laboratory. In 1998, a typhoon struck before rice harvesting in Japan, and the unpolished rice was found to be stained brown. Samples were collected and analyzed for the presence of trichothecenes. Mycotoxins DON, Fus.-X, and NIV were detected and confirmed with GC-MS. The quantity of trichothecenes was determined using GC-ECD. STE is a carcinogenic mycotoxin produced by Aspergillus versicolor and some other fungi. STE contamination of rice was studied in our laboratory since 1973. GC-MS, LC-MS, LC-MS/MS, and LC-UV methods for STE determination were examined, giving good results for the LC-UV method using a photo diode array detector. Different techniques for the extraction of STE from rice were also studied. Finally, brown rice was ground, and the ground rice was extracted with acetonitrile-water. An Autoprep MF-A 1000 column was used to clean up AFS and STE. The cleaned-up extract was analyzed with HPLC-UV. Forty-eight brown rice samples were analyzed, and none of them were contaminated with STE. These rice samples were also analyzed for AFS and FMS, and none of the samples were contaminated. The Ministry of Agriculture, Forestry and Fisheries in Japan is making the appropriate Institutes develop analytical methods for mycotoxins and survey mycotoxin contamination on rice as well as wheat, corn, and some other cereals.
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                Author and article information

                Journal
                J Toxicol Pathol
                J Toxicol Pathol
                TOX
                Journal of Toxicologic Pathology
                Japanese Society of Toxicologic Pathology
                0914-9198
                1881-915X
                30 April 2014
                April 2014
                : 27
                : 1
                : 57-66
                Affiliations
                [1 ] Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
                [2 ] Division of Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
                [3 ] Biological Safety Research Center, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
                [4 ] Laboratory of Food and Hygiene, Department of Food and Life Science, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan
                Author notes
                *Corresponding author: K Inoue (e-mail : k-inoue@ 123456nihs.go.jp )
                Article
                2013-0047
                10.1293/tox.2013-0047
                4000074
                24791068
                3a822376-bf95-4fbe-ae03-90c8270be5ca
                ©2014 The Japanese Society of Toxicologic Pathology

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.

                History
                : 26 August 2013
                : 27 November 2013
                Categories
                Original Article

                Pathology
                nivalenol,renal glomeruli,icgn mice,icr mice,infants
                Pathology
                nivalenol, renal glomeruli, icgn mice, icr mice, infants

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