15-acetyldeoxynivalenol and Vomiting

The type B trichothecenes pollute food crops and have been associated to alimentary toxicosis resulted in emetic reaction in human and animal. This group of mycotoxins consists deoxynivalenol (DON) and four structurally related congeners: 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl deoxynivalenol (15-ADON), nivalenol (NIV) and 4-acetyl-nivalenol (fusarenon X, FX). While emesis induced by intraperitoneally dosed to DON in the mink has been related to plasma up-grading of 5-hydroxytryptamine (5-HT) and neurotransmitters peptide YY (PYY), the impact of oral dosing with DON or its four congeners on secretion of these chemical substances have not been established. The aim of this work was to contraste emetic influence to type B trichothecene mycotoxins by orally dosing and involve these influence to PYY and 5-HT. All five toxins attracted marked emetic reaction that are relevant to elevated PYY and 5-HT. The reduction in vomiting induced by the five toxins and PYY was due to blocking of the neuropeptide Y2 receptor. The inhibition of the induced vomiting response by 5-HT and all five toxins is regulated by the 5-HT3 receptor inhibitor granisetron. In a word, our results indicate that PYY and 5-HT take a key role in the emetic reaction evoked by type B trichothecenes.

Topics: Animals; Emetics; Humans; Mink; Mycotoxins; Peptide YY; Serotonin; Trichothecenes; Trichothecenes, Type B; Vomiting

Although the acute toxic effects of trichothecene mycotoxin deoxynivalenol (DON or vomitoxin), a known cause of human food poisoning, have been well characterized in several animal species, much less is known about closely related 8-ketotrichothecenes that similarly occur in cereal grains colonized by toxigenic fusaria. To address this, we compared potencies of DON, 15-acetyldeoxynivalenol (15-ADON), 3-acetyldeoxynivalenol (3-ADON), fusarenon X (FX), and nivalenol (NIV) in the mink emesis model following intraperitoneal (ip) and oral administration. All five congeners dose-dependently induced emesis by both administration methods. With increasing doses, there were marked decreases in latency to emesis with corresponding increases in emesis duration and number of emetic events. The effective doses resulting in emetic events in 50% of the animals for ip exposure to DON, 15-ADON, 3-ADON, FX, and NIV were 80, 170, 180, 70, and 60 µg/kg bw, respectively, and for oral exposure, they were 30, 40, 290, 30, and 250 µg/kg bw, respectively. The emetic potency of DON determined here was comparable to that reported in analogous studies conducted in pigs and dogs, suggesting that the mink is a suitable small animal model for investigating acute trichothecene toxicity. The use of a mouse pica model, based on the consumption of kaolin, was also evaluated as a possible surrogate for studying emesis but was found unsuitable. From a public health perspective, comparative emetic potency data derived from small animal models such as the mink should be useful for establishing toxic equivalency factors for DON and other trichothecenes.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Female; Injections, Intraperitoneal; Male; Mice; Mink; Mycotoxins; Pica; Toxicity Tests; Trichothecenes; Vomiting

The emetic activity of 15-acetyldeoxynivalenol (15-ADON), a deoxynivalenol (DON) precursor, was evaluated in swine over a dose range of 25-200 micrograms/kg body weight and found to be very similar to that of DON. The minimum effective oral doses for 15-ADON and DON were 75 and 50 micrograms/kg, respectively, with 3/15 of the 15-ADON- and 4/15 of the DON-treated pigs exhibiting emesis, over the total dose range. The minimum effective ip doses for 15-ADON and DON were also 75 and 50 micrograms/kg, respectively, with 9/15 pigs in each group exhibiting emesis, over the total dose range. For pigs receiving 15-ADON and DON ip, increased dosage was associated with decreased average time to vomition, increased duration of emesis and increased average number of vomitions.

Topics: Animals; Dose-Response Relationship, Drug; Regression Analysis; Sesquiterpenes; Swine; Trichothecenes; Vomiting