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Gut satiety hormones cholecystokinin and glucagon-like Peptide-17-36 amide mediate anorexia induction by trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol.

Abstract
The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-17-36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO). The purpose of this study was to relate type A trichothecenes T-2, HT-2, DAS and NEO-induced anorectic response to changes plasma concentrations of CCK and GLP-1. Following both oral gavage and intraperitoneal (IP) administration of 1mg/kg bw T-2, HT-2, DAS and NEO evoked robust anorectic response and secretion of CCK and GLP-1. Elevations of plasma CCK markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Following oral exposure, plasma CCK was peaked at 6h, 6h, 2h, 2h and lasted up to 24h, 24h, > 6h, > 6h for T-2, HT-2, DAS and NEO, respectively. IP exposed to four toxins all induced elevation of CCK with peak point and duration at 6h and >24h, respectively. In contrast to CCK, GLP-1 was moderately elevated by these toxins. Following both oral and IP exposure, T-2 and HT-2 evoked plasma GLP-1 elevation with peak point and duration at 2h and 6h, respectively. Plasma GLP-1 was peaked at 2h and still increased at 6h for IP and oral administration with DAS and NEO, respectively. In conclusion, CCK plays a contributory role in anorexia induction but GLP-1 might play a lesser role in this response.
AuthorsJie Zhang, Shengli Liu, Hua Zhang, Yuanyuan Li, Wenda Wu, Haibin Zhang
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 335 Pg. 49-55 (11 15 2017) ISSN: 1096-0333 [Electronic] United States
PMID28964791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2017 Elsevier Inc. All rights reserved.
Chemical References
  • Peptide Fragments
  • Trichothecenes
  • glucagon-like peptide 1 (7-36)
  • neosolaniol
  • Glucagon-Like Peptide 1
  • Cholecystokinin
  • T-2 Toxin
  • HT-2 toxin
  • diacetoxyscirpenol
Topics
  • Animals
  • Anorexia (blood, chemically induced, prevention & control, psychology)
  • Appetite Regulation
  • Behavior, Animal
  • Cholecystokinin (blood)
  • Disease Models, Animal
  • Feeding Behavior
  • Female
  • Glucagon-Like Peptide 1 (blood)
  • Mice
  • Peptide Fragments (blood)
  • Satiety Response
  • Signal Transduction
  • T-2 Toxin (analogs & derivatives)
  • Time Factors
  • Trichothecenes
  • Up-Regulation

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