Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine
| Autor: | Xiao Pan, James J. Pestka, Wenda Wu, Hui Ren Zhou |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
IL-1β
interleukin-1β Emetine Health Toxicology and Mutagenesis Trichothecene NPY neuropeptide Y POMC pro-opiomelanocortin HT-2 toxin DMSO dimethyl sulfoxide Pharmacology Toxicology medicine.disease_cause MC4R melanocortin 4 receptor TNF-α tumor necrosis factor-α Article SG satratoxin G chemistry.chemical_compound AGRP agouti-related protein NOAELs no adverse effect levels lcsh:RA1190-1270 T-2 toxin medicine Potency CART amphetamine-regulated transcript IL-6 interleukin-6 Mycotoxin lcsh:Toxicology. Poisons DON vomitoxin deoxynivalenol LOAELs lowest adverse effect levels Chemistry Toxin Alkaloid Anorexia Satratoxin G Anorectic Nasal administration medicine.drug |
| Zdroj: | Toxicology Reports Toxicology Reports, Vol 2, Iss C, Pp 238-251 (2015) |
| ISSN: | 2214-7500 |
| DOI: | 10.1016/j.toxrep.2014.12.010 |
| Popis: | Highlights • Anorectic effects of natural toxins were compared in the mouse. • Parenteral and oral T-2 and HT-2 toxin exposure caused prolonged anorexia. • Emetine was more potent when delivered orally as compared to parenterally. • Emetine's effects were less than T-2 and HT-2 toxin and more transient. • Parental and intranasal delivery satratoxin G caused transient anorectic effects. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|