title: Comparison of anorectic and emetic potencies of deoxynivalenol (vomitoxin) to the plant metabolite deoxynivalenol-3-glucoside and synthetic deoxynivalenol derivatives EN139528 and EN139544.
abstract: The mycotoxin deoxynivalenol (DON) elicits robust anorectic and emetic effects in several animal species. However, less is known about the potential for naturally occurring and synthetic congeners of this trichothecene to cause analogous responses. Here we tested the hypothesis that alterations in DON structure found in the plant metabolite deoxynivalenol-3-glucoside (D3G) and two pharmacologically active synthetic DON derivatives, EN139528 and EN139544, differentially impact their potential to evoke food refusal and emesis. In a nocturnal mouse food consumption model, oral administration with DON, D3G, EN139528, or EN139544 at doses from 2.5 to 10 mg/kg BW induced anorectic responses that lasted up to 16, 6, 6, and 3 h, respectively. Anorectic potency rank orders were EN139544>DON>EN139528>D3G from 0 to 0.5 h but DON>D3G>EN139528>EN139544 from 0 to 3 h. Oral exposure to each of the four compounds at a common dose (2.5 mg/kg BW) stimulated plasma elevations of the gut satiety peptides cholecystokinin and to a lesser extent, peptide YY3-36 that corresponded to reduced food consumption. In a mink emesis model, oral administration of increasing doses of the congeners differentially induced emesis, causing marked decreases in latency to emesis with corresponding increases in both the duration and number of emetic events. The minimum emetic doses for DON, EN139528, D3G, and EN139544 were 0.05, 0.5, 2, and 5 mg/kg BW, respectively. Taken together, the results suggest that although all three DON congeners elicited anorectic responses that mimicked DON over a narrow dose range, they were markedly less potent than the parent mycotoxin at inducing emesis.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P.R. China Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824.
authors.forename: Wenda
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824.
authors.forename: Hui-Ren
authors.initials: HR
authors.lastname: Zhou
authors.affiliation: Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 Department of Animal Science, Michigan State University, East Lansing, Michigan 48824.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bursian
authors.affiliation: Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824.
authors.forename: Xiao
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Animal Science, Michigan State University, East Lansing, Michigan 48824.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Link
authors.affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Vienna, 3430 Tulln, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Berthiller
authors.affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, 3430 Tulln, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Adam
authors.affiliation: Cellular and Molecular Medicine, University of Ottawa, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Krantis
authors.affiliation: Department of Chemistry, University of Ottawa, Canada.
authors.forename: Tony
authors.initials: T
authors.lastname: Durst
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824 Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 Department of Animal Science, Michigan State University, East Lansing, Michigan 48824 pestka@msu.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Pestka
mesh_terms: D000818:Animals; D000855:Anorexia / Q000097:blood / Q000139:chemically induced*; D002766:Cholecystokinin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005260:Female; D005960:Glucosides / Q000737:chemistry / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008815:Mice, Inbred Strains; D008907:Mink; D015394:Molecular Structure; D019055:No-Observed-Adverse-Effect Level; D010446:Peptide Fragments / Q000097:blood; D019894:Peptide YY / Q000097:blood; D014255:Trichothecenes / Q000737:chemistry / Q000633:toxicity*; D014839:Vomiting / Q000097:blood / Q000139:chemically induced*
chemical_list: C000599401:EN139528; C000599402:EN139544; D005960:Glucosides; D010446:Peptide Fragments; D014255:Trichothecenes; C542050:deoxynivalenol-3-glucoside; D019894:Peptide YY; C061785:peptide YY (3-36); D002766:Cholecystokinin; C007262:deoxynivalenol
keywords: 5-hydroxytryptamine; EN139528; EN139544; anorexia; cholecystokinin; deoxynivalenol; deoxynivalenol-3-glucoside; emesis; mycotoxin; peptide YY3–36