title: Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3-36 and 5-hydroxytryptamine.
abstract: Trichothecene mycotoxins are a family of potent translational inhibitors that are associated with foodborne outbreaks of human and animal gastroenteritis in which vomiting is a clinical hallmark. Deoxynivalenol (DON, vomitoxin) and other Type B trichothecenes have been previously demonstrated to cause emesis in the mink (Neovison vison), and this response has been directly linked to secretion of both the satiety hormone peptide YY3-36 (PYY3-36) and neurotransmitter 5-hydroxytryptamine (5-HT). Here, we characterized the emetic responses in the mink to T-2 toxin (T-2) and HT-2 toxin (HT-2), two highly toxic Type A trichothecenes that contaminate cereals, and further compared these effects to those of emetine, a natural alkaloid that is used medicinally and also well known to block translation and cause vomiting. Following intraperitoneal (IP) and oral exposure, all three agents caused vomiting with evident dose-dependent increases in both duration and number of emetic events as well as decreases in latency to emesis. T-2 and HT-2 doses causing emesis in 50 % of treated animals (ED50s) were 0.05 and 0.02 mg/kg BW following IP and oral administration, respectively, whereas the ED50s for emetine were 2.0 and 1.0 mg/kg BW for IP and oral exposure, respectively. Importantly, oral administration of all three toxins elicited marked elevations in plasma concentrations of PYY3-36 and 5-HT that corresponded to emesis. Taken together, the results suggest that T-2 and HT-2 were much more potent than emetine and that emesis induction by all three translational inhibitors co-occurred with increases in circulating levels of PYY3-36 and 5-HT.
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.|Department of Food Science and Human Nutrition, Michigan State University, 234 G.M. Trout Building, East Lansing, MI, 48824-1224, USA.
authors: Wenda
authors: W
authors: Wu
authors: Department of Food Science and Human Nutrition, Michigan State University, 234 G.M. Trout Building, East Lansing, MI, 48824-1224, USA.
authors: Hui-Ren
authors: HR
authors: Zhou
authors: Center for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA.|Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA.
authors: Steven J
authors: SJ
authors: Bursian
authors: Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA.
authors: Jane E
authors: JE
authors: Link
authors: Department of Food Science and Human Nutrition, Michigan State University, 234 G.M. Trout Building, East Lansing, MI, 48824-1224, USA. pestka@msu.edu.|Center for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA. pestka@msu.edu.|Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA. pestka@msu.edu.
authors: James J
authors: JJ
authors: Pestka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004639:Emetics / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D004640:Emetine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D008907:Mink; D010446:Peptide Fragments / Q000097:blood*; D019894:Peptide YY / Q000097:blood*; D012701:Serotonin / Q000097:blood*; D013605:T-2 Toxin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D014839:Vomiting / Q000139:chemically induced*
chemical_list: D004639:Emetics; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36); D012701:Serotonin; D013605:T-2 Toxin; C012351:HT-2 toxin; D004640:Emetine
keywords: Emesis; Emetine; HT-2 toxin; Mycotoxin; T-2 toxin; Trichothecene