The efficacy of various classes of anti‐emetics in preventing deoxynivalenol‐induced vomiting in swine

Abstract

The Fusarium mycotoxin deoxynivalenol (DON) is a potent emetic agent. While the basic mechanisms which invoke and mediate emesis are still poorly understood, various neurotransmitters appear to be involved. The action of these transmitters can be blocked by various receptor-specific antagonists. The current study investigated the efficacy of several classes of receptor antagonists to block the emetic effect of DON. Following anti-emetic pretreatment, pigs were administered the toxin (i.v., 80 micrograms/kg, or oral, 300 micrograms/kg) and the onset of emesis was monitored. Certain specific serotonin (5HT3)-receptor antagonists (ICS 205-930, BRL 43694 A) were found to efficaciously prevent DON-induced vomiting. These observations support the hypothesis that serotonin plays an important role in chemically induced emesis. Also moderately effective, but requiring high doses, were the 5HT2-receptor antagonists, cyproheptadine and sulpiride. A variety of compounds possessing strong anticholinergic activity were also efficacious. These, however, apparently act directly at the emetic center and thus are capable of preventing emesis regardless of the cause, including chemically induced vomiting. Non-effective were the antihistaminic and antidopaminergic anti-emetics; except, those which also possessed considerable anticholinergic activity, and i.v. administered chlorpromazine which has been speculated to block specific receptors found in the brain's chemoreceptor trigger zone (CTZ) reportedly involved in initiating emesis.

Effects of Potential Detoxifying Agents on Growth Performance and Deoxynivalenol (DON) Urinary Balance Characteristics of Nursery Pigs Fed DON-Contaminated Wheat

“…The present data agree with Etienne and Waché (2008), who cited a 4.6% decrease in ADFI for every 1 mg/kg of DON in the diet, and Frobose et al (2015), who described the feed intake suppression pattern as being the most marked during the initial exposure period and lessening over time. The anorexic effects of DON are most frequently attributed to changes in the metabolism and concentration of brain neurotransmitters such as serotonin in cerebrospinal fluid (Prelusky and Trenholm, 1993;Prelusky, 1994), causing delayed gastric emptying and decreasing small-intestinal motility (Rotter et al, 1996). Moreover, pigs develop conditioned taste aversion to DON-contaminated feedstuffs (Ossenkopp et al, 1994), which is consistent with observations of feed refusal and general anxiety in pigs fed DON (Bergsjo et al, 1993;Dänicke et al, 2004a).…”

Modeling the emetic potencies of food-borne trichothecenes by benchmark dose methodology

“…This is because the vomiting center in the brain is stimulated when either the receptors in the periphery (gastrointestinal tract) or in the blood are activated by the presence of toxins (Horn, 2008; Prelusky and Trenholm, 1993). Studies have shown that trichothecenes cause gastroenteritis (Pestka, 2010), which activates the enterochromaffin cells in the epithelium to release 5-hydroxytryptamine (5-HT) or serotonin.…”

“…Studies have shown that trichothecenes cause gastroenteritis (Pestka, 2010), which activates the enterochromaffin cells in the epithelium to release 5-hydroxytryptamine (5-HT) or serotonin. The 5-HT neurotransmitter sends signals to the brain vomiting center to induce vomiting (Prelusky and Trenholm, 1993). Likewise, introduction of toxins into the blood by IP dosing or absorption from the gut into the systemic circulation can stimulate the vomiting center via direct activation of 5-HT 3 receptors in the chemoreceptor trigger zone (CTZ) in the brain (Becker, 2010; Dietrich et al, 2015; Kovac, 2016; Horn, 2008; Lang, 1999; Prelusky and Trenholm, 1993).…”

Overview of investigations into pulmonary hemorrhage among infants in Cleveland, Ohio.

“…Although these specific toxins have not been as extensively studied as the trichothecenes deoxynivalenol and T-2 toxin, their mechanism of toxicity is thought to be very similar or the same. High-dose exposure to deoxynivalenol causes emesis and myocardial and gastrointestinal hemorrhages; lower exposures cause damage to the immune system, affect the appetite center of the brain, and alter neurotransmitter levels (24)(25)(26)(27). Primarily because of the immunotoxicity of deoxynivalenol, there are guidelines on the amount of this mycotoxin allowed in wheat in the United States and Canada (28).…”