Emetic Response to T-2 Toxin Correspond to Secretion of Glucagon-like Peptide-17–36 Amide and Glucose-Dependent Insulinotropic Polypeptide

Abstract

The T-2 toxin, a major secondary metabolite of Fusarium Gramineae, is considered a great risk to humans and animals due to its toxicity, such as inducing emesis. The mechanism of emesis is a complex signal involving an imbalance of hormones and neurotransmitters, as well as activity of visceral afferent neurons. The T-2 toxin has been proven to induce emesis and possess the capacity to elevate expressions of intestinal hormones glucagon-like peptide-17–36 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), both of which are important emetic factors. In addition, the activation of calcium-sensitive receptor (CaSR) and transient receptor potential (TRP) channels are engaged in intestinal hormone release. However, it is unknown whether hormones GLP-1 and GIP mediate T-2 toxin-induced emetic response through activating CaSR and TRP channels. To further assess the mechanism of T-2 toxin-induced emesis, we studied the hypothesis that T-2 toxin-caused emetic response and intestinal hormones GLP-1 and GIP released in mink are associated with activating calcium transduction. Following oral gavage and intraperitoneal injection T-2 toxin, emetic responses were observed in a dose-dependent manner, which notably corresponded to the secretion of GLP-1 and GIP, and were suppressed by pretreatment with respective antagonist Exending9–39 and Pro3GIP. Additional research found that NPS-2143 (NPS) and ruthenium red (RR), respective antagonists of CaSR and TRP channels, dramatically inhibited both T-2 toxin-induced emesis response and the expression of plasma GLP-1 and GIP. According to these data, we observed that T-2 toxin-induced emetic response corresponds to secretion of GLP-1 and GIP via calcium transduction.

Remediation Strategies for Mycotoxins in Animal Feed

“…Specifically, Yuan et al found that low-dose dietary ZEN (750 μg/kg) could reduce production performance, ovarian function and intestinal microbes in laying hens via dysregulation of gut microbes; and their study indicated that g_norank_f_Barnesiellaceae , g_Hydrogenoanaerobacterium and g_Butyricmonas showed a positive correlation with production performance, egg quality and (or) ovarian function [ 31 ]. Notably, the novel toxicity of trichothecene mycotoxin has been reported by Wenda Wu’s group [ 32 , 33 , 34 , 35 , 36 ]. Specifically, T-2 toxin-induced emetic response showed a correlation with the secretion of the intestinal hormones glucagon-like peptide -17–36 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) mediated by calcium transduction.…”

“…Specifically, T-2 toxin-induced emetic response showed a correlation with the secretion of the intestinal hormones glucagon-like peptide -17–36 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) mediated by calcium transduction. Furthermore, suppression of the calcium-sensitive receptor (CaSR) and transient receptor potential (TRP) channels alleviated emesis by their antagonists NPS-2143 and ruthenium red in mink [ 32 ]. Similarly, DON-3-glucoside (D3G), which co-occurs with DON, could also trigger marked emesis via the exocytosis of brain–gut peptides GIP and substance (SP); additionally, the GIP and neurokinin 1 receptor (NK-1R) are potential targets to diminish the intestinal emetic response [ 33 ].…”

“…An anorexic response, caused by trichothecene A (T-2 toxin, HT-2 toxin, diacetoxyscripenol and neosolaniol, and trichothecene B DON) and its congeners (DON, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, fusarenon X and nivalenol), was associated with the generation of GLP-1 and cholecystokinin (CCK) or SP, which could be suppressed by the Exending 9–39 CCK antagonist (Sigma-Aldrich, St. Louis, MO, USA) and Emend ® (Merck& Co, Inc, Kenilworth, NJ, USA) [ 34 , 35 , 36 ]. To summarize, gastrointestinal vomiting and anorexia caused by trichothecene mycotoxins are usually related to the release of brain–gut peptides GLP-1, GIP and SP, and the remediation measures can take CaSR and TRP channels as well as NK-1R and GLP-1R into consideration [ 32 , 33 , 34 , 35 , 36 ]. Liu et al revealed that T-2 toxin-induced intestinal damage was associated with an alteration in nucleotide and glyceropholipid metabolism, redox homeostasis and apoptosis, which accounted for intestinal damage in chicken [ 37 ].…”