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Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3–36 and 5-hydroxytryptamine

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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.

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References

  • Andrews PL, Horn CC (2006) Signals for nausea and emesis: implications for models of upper gastrointestinal diseases. Auton Neurosci 125(1):100–115

    Article  PubMed  PubMed Central  Google Scholar 

  • Beasley VR, Swanson SP, Corley RA, Buck WB, Koritz GD, Burmeister HR (1986) Pharmacokinetics of the trichothecene mycotoxin, T-2 toxin, in swine and cattle. Toxicon 24(1):13–23

    Article  CAS  PubMed  Google Scholar 

  • Bhargava K, Gupta P, Chandra O (1961) Effect of ablation of the chemoreceptor trigger zone (CT zone) on the emetic response to intraventricular injection of apomorphine and emetine in the dog. J Pharmacol Exp Ther 134(3):329–331

    CAS  PubMed  Google Scholar 

  • Borison HL, Goodheart ML (1989) Neural factors in acute emetic, cardiovascular, and respiratory effects of T-2 toxin in cats. Toxicol Appl Pharmacol 101(3):399–413

    Article  CAS  PubMed  Google Scholar 

  • Boyd EM, Knight LM (1964) The expectorant action of cephaeline, emetine and 2-dehydroemetine. J Pharm Pharmacol 16(2):118–124

    Article  CAS  PubMed  Google Scholar 

  • Child K, Davis B, Dodds M, Tomich E (1964) Toxicity and tissue distribution studies on the hydrochloride, bismuth iodide complex and a resinate of emetine. J Pharm Pharmacol 16(2):65–71

    Article  CAS  PubMed  Google Scholar 

  • Ellison RA, Kotsonis FN (1973) T-2 toxin as an emetic factor in moldy corn. Appl Microbiol 26(4):540–543

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ellison RA, Kotsonis FN (1974) In vitro metabolism of T-2 toxin. Appl Microbiol 27(2):423–424

    CAS  PubMed  PubMed Central  Google Scholar 

  • Endo T, Minami M, Hirafuji M et al (2000) Neurochemistry and neuropharmacology of emesis—the role of serotonin. Toxicology 153(1):189–201

    Article  CAS  PubMed  Google Scholar 

  • Fairhurst S, Marrs T, Parker H, Scawin J, Swanston D (1987) Acute toxicity of T2 toxin in rats, mice, guinea pigs, and pigeons. Toxicology 43(1):31–49

    Article  CAS  PubMed  Google Scholar 

  • Ferrari F, Ottani A, Giuliani D (1999) Cannabimimetic activity in rats and pigeons of HU 210, a potent antiemetic drug. Pharmacol Biochem Behav 62:75–80

    Article  CAS  PubMed  Google Scholar 

  • Forsyth D, Yoshizawa T, Morooka N, Tuite J (1977) Emetic and refusal activity of deoxynivalenol to swine. Appl Environ Microbiol 34(5):547–552

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fur Commission USA. 2010. Standard guidelines for the operation of mink farms in the US. http://www.maninnature.com/FCUSA/Members/Resources/Minkguide.pdf. Last accessed November 18, 2014

  • Gaige S, Djelloul M, Tardivel C et al (2014) Modification of energy balance induced by the food contaminant T-2 toxin: a multimodal gut-to-brain connection. Brain Behav Immun 37:54–72. doi:10.1016/j.bbi.2013.12.008

    Article  CAS  PubMed  Google Scholar 

  • Greenway J, Puls R (1976) Fusariotoxicosis from barley in British Columbia. I. Natural occurrence and diagnosis. Can J Comp Med 40(1):12–15

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta RS, Siminovitch L (1977) The molecular basis of emetine resistance in Chinese hamster ovary cells: alteration in the 40S ribosomal subunit. Cell 10(1):61–66

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa M, Sasaki T, Sadakane K et al (2002) Studies for the emetic mechanisms of ipecac syrup (TJN-119) and its active components in ferrets: involvement of 5-hydroxytryptamine receptors. Jpn J Pharmacol 89(2):113–119

    Article  CAS  PubMed  Google Scholar 

  • Hornby PJ (2001) Central neurocircuitry associated with emesis. Am J Med 111(8):106–112

    Article  Google Scholar 

  • Hsu I-C, Smalley E, Strong F, Ribelin WE (1972) Identification of T-2 toxin in moldy corn associated with a lethal toxicosis in dairy cattle. Appl Microbiol 24(5):684–690

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson LS, Bullerman LB (1999) Effect of processing on Fusarium mycotoxins. Impact Process Food Saf 459:243–261

    Article  CAS  Google Scholar 

  • JECFA (2002) Evaluation of certain mycotoxins in food: 56th report of the joint FAO/WHO expert committee on food additives WHO technical report series. vol 906, pp 42–51

  • Kalantari H, Moosavi M (2010) Review on T-2 toxin. Jundishapur Journal of Natural Pharmaceutical Products(5):26-38

  • Kris MG, Hesketh PJ, Somerfield MR et al (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24(18):2932–2947

    Article  CAS  PubMed  Google Scholar 

  • Leatherman DL, Middlebrook JL (1993a) Effect of emetine on T-2 toxin-induced inhibition of protein synthesis in mammalian cells. J Pharmacol Exp Ther 266(2):741–748

    CAS  PubMed  Google Scholar 

  • Leatherman DL, Middlebrook JL (1993b) Effects of emetine on the specific association of T-2 toxin with mammalian cells. J Pharmacol Exp Ther 266(2):732–740

    CAS  PubMed  Google Scholar 

  • Luo X (1994) Food poisoning caused by Fusarium toxins. In: Proceedings of the Second Asian Conference on Food Safety. International Life Sciences Institute. Chatuchak, Thailand, pp 129–136

  • Lutsky I, Mor N (1981a) Alimentary toxic aleukia (septic angina, endemic panmyelotoxicosis, alimentary hemorrhagic aleukia): t-2 toxin-induced intoxication of cats. Am J Pathol 104(2):189–191

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lutsky I, Mor N (1981b) Experimental alimentary toxic aleukia in cats. Lab Anim Sci 31(1):43–47

    CAS  PubMed  Google Scholar 

  • Neal R (1983) Experimental amoebiasis and the development of anti-amoebic compounds. Parasitology 86(01):175–191

    Article  CAS  PubMed  Google Scholar 

  • Osselaere A, Devreese M, Goossens J et al (2013) Toxicokinetic study and absolute oral bioavailability of deoxynivalenol, T-2 toxin and zearalenone in broiler chickens. Food Chem Toxicol 51:350–355

    Article  CAS  PubMed  Google Scholar 

  • Perry M, Rhee J, Smith W (1994) Plasma levels of peptide YY correlate with cisplatin-induced emesis in dogs. J Pharm Pharmacol 46(7):553–557

    Article  CAS  PubMed  Google Scholar 

  • Pestka J (2010a) Toxicological mechanisms and potential health effects of deoxynivalenol and nivalenol. World Mycotox J 3(4):323–347

    Article  CAS  Google Scholar 

  • Pestka JJ (2010b) Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Arch Toxicol 84(9):663–679

    Article  CAS  PubMed  Google Scholar 

  • Pestka J, Lin W-S, Miller E (1987) Emetic activity of the trichothecene 15-acetyldeoxynivalenol in swine. Food Chem Toxicol 25(11):855–858

    Article  CAS  PubMed  Google Scholar 

  • Prelusky DB, Trenholm HL (1993) The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swine. Nat Toxins 1(5):296–302

    Article  CAS  PubMed  Google Scholar 

  • Qian QH, Yue W, Wang YX, Yang ZH, Liu ZT, Chen WH (2009) Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks. Arch Pharm Res 32(4):565–573. doi:10.1007/s12272-009-1413-9

    Article  CAS  PubMed  Google Scholar 

  • Qian Q, Chen W, Yue W, Yang Z, Liu Z, Qian W (2010a) Antiemetic effect of Xiao-Ban-Xia-Tang, a Chinese medicinal herb recipe, on cisplatin-induced acute and delayed emesis in minks. J Ethnopharmacol 128(3):590–593. doi:10.1016/j.jep.2010.01.027

    Article  PubMed  Google Scholar 

  • Qian QH, Yue W, Chen WH, Yang ZH, Liu ZT, Wang YX (2010b) Effect of gingerol on substance P and NK1 receptor expression in a vomiting model of mink. Chin Med J (Engl) 123(4):478–484

    CAS  Google Scholar 

  • Sato N, Ueno Y, Enomoto M (1975) Toxicological approaches to the toxic metabolites of Fusaria. VIII. Acute and subacute toxicities of T-2 toxin in cats. JPN J Pharmacol 25(3):263–270

    Article  CAS  PubMed  Google Scholar 

  • SCF (2002) Opinion of the Scientific Committee on Food on Fusarium toxins. Part 6: group evaluation of T-2 toxin, HT-2 toxin, nivalenol and deoxynivalenol European Commission, Brussels, Belgium. http://ec.europa.eu/food/fs/sc/scf/out123_en.pdf. Accessed 3 April 2015

  • Schothorst RC, van Egmond HP (2004) Report from SCOOP task 3.2.10 “collection of occurrence data of Fusarium toxins in food and assessment of dietary intake by the population of EU member states”. Subtask: trichothecenes. Toxicol Lett 153(1):133–143

    Article  CAS  PubMed  Google Scholar 

  • Sintov A, Bialer M, Yagen B (1986) Pharmacokinetics of T-2 toxin and its metabolite HT-2 toxin, after intravenous administration in dogs. Drug Metab Dispos 14(2):250–254

    CAS  PubMed  Google Scholar 

  • Ueno Y (1977) Mode of action of trichothecenes. Pure Appl Chem 49(11):1737–1745

    Article  CAS  Google Scholar 

  • Ueno Y (1987) Trichothecenes in food. Mycotoxins in food:123-147

  • Ueno Y, Sato N, Ishii K, Sakai K, Tsunoda H, Enomoto M (1973) Biological and chemical detection of trichothecene mycotoxins of Fusarium species. Appl Microbiol 25(4):699–704

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wolff MC, Leander JD (1995) Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3 antagonists in the pigeon. Pharmacol Biochem Behav 52(3):571–575

    Article  CAS  PubMed  Google Scholar 

  • Wong W, Bai XC, Brown A et al (2014) Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. Elife. doi:10.7554/eLife.03080

    Google Scholar 

  • Wu W, Bates MA, Bursian SJ et al (2013a) Comparison of emetic potencies of the 8-ketotrichothecenes deoxynivalenol, 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, fusarenon X and nivalenol. Toxicol Sci 131(1):279–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu W, Bates MA, Bursian SJ et al (2013b) Peptide YY3–36 and 5-hydroxytryptamine mediate emesis Induction by trichothecene deoxynivalenol (vomitoxin). Toxicol Sci 133(1):186–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu W, Zhou HR, Bursian SJ et al (2014) Comparison of anorectic and emetic potencies of deoxynivalenol (vomitoxin) to the plant metabolite deoxynivalenol-3-glucoside and synthetic deoxynivalenol derivatives EN139528 and EN139544. Toxicol Sci 142(1):167–181. doi:10.1093/toxsci/kfu166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yen M, Ewald MB (2012) Toxicity of weight loss agents. J Med Toxicol 8(2):145–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshizawa T (1983) Trichothecenes: chemical, biological, and toxicological aspects. Kodansha Ltd., Tokyo, pp 195–209

    Google Scholar 

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Acknowledgments

We would like to acknowledge the assistance of Angelo Napolitano, Erica Clark and Mary Rosner. This study was supported by USDA NIFA Award (2011-0635), USDA Wheat and Barley SCAB Initiative Award 59-0206-9-058 and by Public Health Service Grant ES03553 from the National Institutes of Health. W.W. was supported by National Natural Science Foundation of China (31402268), the Priority Academic Development Program of Jiangsu Higher Education Institutions, Natural Science Foundation of Jiangsu Province of China (BK20140691).

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Authors and Affiliations

  1. College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China

    Wenda Wu

  2. Department of Food Science and Human Nutrition, Michigan State University, 234 G.M. Trout Building, East Lansing, MI, 48824-1224, USA

    Wenda Wu, Hui-Ren Zhou & James J. Pestka

  3. Center for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA

    Steven J. Bursian & James J. Pestka

  4. Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA

    James J. Pestka

  5. Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA

    Steven J. Bursian & Jane E. Link

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  1. Wenda Wu
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Correspondence to James J. Pestka.

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Wu, W., Zhou, HR., Bursian, S.J. et al. Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3–36 and 5-hydroxytryptamine. Arch Toxicol 90, 997–1007 (2016). https://doi.org/10.1007/s00204-015-1508-7

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