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    Immunosuppressive effects of fumonisin B1 in the Trichinella spiralis model

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    Authors
    Nijs M de
    Egmond HP van
    Jong WH de
    Loveren H van
    Series/Report no.
    RIVM Rapport 388802017
    Type
    Report
    Report
    Language
    en
    
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    Title
    Immunosuppressive effects of fumonisin B1 in the Trichinella spiralis model
    Translated Title
    Vaststellen van immuunsuppressieve effecten van fumonisine B1 in het Trichinella spiralis model
    Publiekssamenvatting
    Fumonisin B1 is a mycotoxin produced by Fusarium moniliforme and is found mainly in maize. Fumonisin B1 has been associated with human esophageal cancer, lung edema in pigs and leuko-encephalomalacia in equine species. Adverse effects of this mycotoxin on the immune system can be expected but were currently only reported in chickens and mice. The toxic effects of this mycotoxin in male rats has been studied in a 28-day toxicity study (TIER I) in the RIVM:WU rat (AAP protocol 199600652). The weight of the kidneys of animals in the high-dose group significantly decreased as compared to weights of kidneys of animals in the lower dose and control groups. Pathological effects were observed in the kidneys of animals of all dose groups. Dose-related single-cell necrosis was observed in all dose groups. The activity of gamma-GT was significantly increased in animals in the highest dose group. No direct immunotoxic effect was observed; however, there was a trend for an increased concentration of B-cells in animals in the highest dose group. In a functional assay (Trichinella spiralis infection) the effect of low doses of fumonisin B1 on the immmune system was studied. Male rats (age three weeks) received oral (gavage) doses of 0, 0.05, 0.19 or 0.75 mg fumonisin B1 kg-1 body weight (BW) (dissolved in water) daily for 10 weeks. All animals were infected with larvae of the Trichinella spiralis on day 28. After 70 days of treatment, the animals were sacrificed and necropsied. Immunoglobulins were determined in the blood. Larvae were counted in the whole carcass and tongue tissue.The growth of animals of the treatment groups decreased, but not statistically significant, when compared to growth of animals in the control group. All immunogobulin levels decreased, IgG and IgM statistically significant, in animals of the medium and high-dose groups as compared to animals of the control group. IgG statistically significantly decreased in the low-dose groups as compared to animals of the control group. The relative amount of T. spiralis larvae in tongue muscle increased in animals of all treatment groups; statistical significance was observed in the lowest and highest dose group. No differences in inflammatory reaction surrounding the larvae in the tongue muscle were observed. Total count of larvae present in the carcasses was increased in animals in the medium and high-dose groups (not statistically significant). It was lowered in the low dose group. Thus, a trend was observed for increased counts of larvae when the animals were exposed to higher levels of fumonisin B1.The immune system of rats is functionally affected after chronic exposure to low doses fumonisin B1.
    Fumonisine B1 is een mycotoxine geproduceerd door Fusarium moniliforme en wordt vooral gevonden in mais. Fumonisine B1 veroorzaakt oesophaguskanker in de mens, longoedeem in het varken en leuko-encephalomalacie in het paard. Effecten van dit mycotoxine op het immuunsysteem werden waargenomen in de kip en de muis. Het toxische effect van fumonisine B1 werd bestudeerd in een 28-daagse toxiciteitsstudie in de RIVM:WU rat. In dat experiment werd het gewicht van de nieren in de hoogste doseringsgroepen significant verlaagd. Dosisgerelateerde pathologische effecten (celnecrose) werden gevonden in nieren van alle doseringsgroepen. Het effect van gamma-GT was significant verhoogd in dieren uit de hoogste doseringsgroepen. Geen direct immunotoxisch effect werd waargenomen, hoewel er een trend werd gezien in toegenomen B-cel aantallen in dieren uit de hoogste doseringsgroepen.In deze studie werd het effect van lage doseringen fumonisine B1 op het immuunsysteem bestudeerd met behulp van een functionele assay, het Trichinella spiralis infectiemodel. Mannetjesratten van drie weken oud werden oraal via maagsonde behandeld met 0, 0,05, 0,19 of 0,75 mg fumonisine B1 per kg lichaamsgewicht dagelijks gedurende 10 weken. Vervolgens werden alle dieren oraal genfecteerd met Trichinella spiralis larven. Zeventig dagen na het begin van het experiment werden dieren opgeofferd, antilichamen werden in het bloed gemeten, terwijl Trichinella spiralis larven in het karkas en tongweefsel werden gemeten. Het gewicht van de dieren in alle behandelde groepen was wat afgenomen, echter de afname was niet statistisch significant. IgE- en IgG-antilichaamtiters waren statistisch significant afgenomen in de midden en hogere doseringsgroepen, terwijl de IgG-antistoftiter ook significant was afgenomen in de laagste doseringsgroep. Het aantal Trichinella spiralis larven in tongweefsel was statistisch significant toegenomen in alle doseringsgroepen. De ontstekingsreactie om larven in tongweefsel waren kwalitatief en kwantitatief niet beinvloed door fumonisine B1 blootstelling en in het gehele karkas werden toegenomen aantallen Trichinella spiralis larven gezien, doch deze toename was niet significant. Het immuunsysteem van ratten wordt nadelig beinvloed in zijn functie naar chronische expositie aan lage doseringen van fumonisine B1.
    Publisher
    Rijksinstituut voor Volksgezondheid en Milieu RIVM
    URI
    http://hdl.handle.net/10029/10001
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