Comparison of Anorectic Potencies of the Trichothecenes T-2 Toxin, HT-2 Toxin and Satratoxin G to the Ipecac Alkaloid Emetine.
Trichothecene mycotoxins, potent translational inhibitors that are associated with human food poisonings and damp-building illnesses, are of considerable concern to animal and human health. Food refusal is a hallmark of exposure of experimental animals to deoxynivalenol (DON) and other Type B trichothecenes but less is known about the anorectic effects of foodborne Type A trichothecenes (e.g., T-2 toxin, HT-2 toxin), airborne Type D trichothecenes (e.g. satratoxin G [SG]) or functionally analogous metabolites that impair protein synthesis. Here, we utilized a well-described mouse model of food intake to compare the anorectic potencies of T-2 toxin, HT-2 toxin, and SG to that of emetine, a medicinal alkaloid derived from ipecac that inhibits translation. Intraperitoneal (IP) administration with T-2 toxin, HT-2 toxin, emetine and SG evoked anorectic responses that occurred within 0.5 h that lasted up to 96, 96, 3 and 96 h, respectively, with lowest observed adverse effect levels (LOAELs) being 0.1, 0.1, 2.5 and 0.25 mg/kg BW, respectively. When delivered via natural routes of exposure, T-2 toxin, HT-2 toxin, emetine (oral) and SG (intranasal) induced anorectic responses that lasted up to 48, 48, 3 and 6 h, respectively with LOAELs being 0.1, 0.1, 0.25, and 0.5 mg/kg BW, respectively. All four compounds were generally much more potent than DON which was previously observed to have LOAELs of 1 and 2.5 mg/kg BW after IP and oral dosing, respectively. Taken together, these anorectic potency data will be valuable in discerning the relative risks from trichothecenes and other translational inhibitors of natural origin.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P.R. China ; Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.
Wenda
W
Wu
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.
Hui-Ren
HR
Zhou
Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Xiao
X
Pan
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA ; Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
James J
JJ
Pestka
Anorexia; Emetine; HT-2 toxin; Satratoxin G; T-2 toxin; Trichothecene