title: Short-term moderate aflatoxin B1 exposure has only minor effects on the gut-associated lymphoid tissue of Brown Norway rats.
abstract: Aflatoxin B1 (AFB1) is toxic to the systemic immune system in various animal species, whereas little is known about its effect on the gut-associated lymphoid tissue (GALT). It may be hypothesized that the toxicity of AFB1 and its locally generated metabolites in the intestinal tissue may result in a disturbed intestinal integrity and, subsequently, in an impaired immune response towards dietary proteins. The objective of our study was to investigate the toxic effect of short-term moderate AFB1 exposure on the intestinal epithelium and on the immune cells associated with the intestinal tract. The toxicological potential of AFB1 and its metabolites to the intestinal epithelium was determined by measuring viability and genotoxic damage in isolated jejunal epithelial cells (comet assay) after 30 min incubation in vitro. In vivo toxicology studies were carried out with Brown Norway (BN) rats, which were exposed orally once a week with AFB1 (1 x 100 microg/kg body weight (b.w.)/week) for 5 consecutive weeks. Viability and genotoxicity were measured in explanted jejunal epithelial cells. For studying the effectiveness of AFB1 on immunological parameters BN rats were treated with a high (study 1: 1 x 1 mg/kg b.w./week) or a low (study 2: 1 x 100 microg/kg b.w./week) AFB1 dose for 5 consecutive weeks with or without ovalbumin (OVA). Mesenteric lymphocytes were isolated and proliferative responsiveness, secretion of interferon-gamma, and changes in lymphocyte subpopulations as well as mucosal mast cell specific protease and anti-OVA specific antibody concentrations were measured. In vitro, AFB1 ( >30 microM) induced genotoxicity in rat jejunal epithelial cells. The oral administration of AFB1 (1 x 100 microg/kg b.w./week) did not induce DNA damage in jejunal epithelial cells. The high AFB1 dose increased the number of CD8+ and CD8/CD71 + cells in mesenteric lymph nodes. The immune response towards OVA was not affected. The low AFB1 dose only reduced the proliferative responsiveness of mesenteric lymphocytes (P < 0.05). Serum concentrations of anti-OVA specific IgE antibody, of RMCPII, and the capacity of mesenteric lymphocytes to produce interferon-gamma were not impaired by AFB1. In conclusion, exposure to moderate doses of AFB1 does not damage the intestinal epithelium and has only minor effects on the GALT. The low exposure, as it may predominantly occur in western countries, does not appear to increase the risk for sensitization to dietary antigens.
authors.affiliation: Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany. bernhard.watzl@bfe.uni-karlsruhe.de
authors.forename: B
authors.initials: B
authors.lastname: Watzl
authors.forename: C
authors.initials: C
authors.lastname: Neudecker
authors.forename: G M
authors.initials: GM
authors.lastname: Hänsch
authors.forename: G
authors.initials: G
authors.lastname: Rechkemmer
authors.forename: B L
authors.initials: BL
authors.lastname: Pool-Zobel
mesh_terms: D016604:Aflatoxin B1 / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007372:Interferons / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000201:enzymology; D008643:Mesentery; D008666:Metalloendopeptidases / Q000378:metabolism; D009152:Mutagenicity Tests; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D007372:Interferons; D016604:Aflatoxin B1; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus