Cargando…
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 tricho...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410735/ https://www.ncbi.nlm.nih.gov/pubmed/25932382 http://dx.doi.org/10.1016/j.toxrep.2014.12.010 |
_version_ | 1782368371214385152 |
---|---|
author | Wu, Wenda Zhou, Hui-Ren Pan, Xiao Pestka, James J. |
author_facet | Wu, Wenda Zhou, Hui-Ren Pan, Xiao Pestka, James J. |
author_sort | Wu, Wenda |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4410735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-44107352016-01-01 Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine Wu, Wenda Zhou, Hui-Ren Pan, Xiao Pestka, James J. Toxicol Rep Article 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. Elsevier 2015-01-02 /pmc/articles/PMC4410735/ /pubmed/25932382 http://dx.doi.org/10.1016/j.toxrep.2014.12.010 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Wu, Wenda Zhou, Hui-Ren Pan, Xiao Pestka, James J. Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine |
title | Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine |
title_full | Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine |
title_fullStr | Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine |
title_full_unstemmed | Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine |
title_short | Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine |
title_sort | comparison of anorectic potencies of the trichothecenes t-2 toxin, ht-2 toxin and satratoxin g to the ipecac alkaloid emetine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410735/ https://www.ncbi.nlm.nih.gov/pubmed/25932382 http://dx.doi.org/10.1016/j.toxrep.2014.12.010 |
work_keys_str_mv | AT wuwenda comparisonofanorecticpotenciesofthetrichothecenest2toxinht2toxinandsatratoxingtotheipecacalkaloidemetine AT zhouhuiren comparisonofanorecticpotenciesofthetrichothecenest2toxinht2toxinandsatratoxingtotheipecacalkaloidemetine AT panxiao comparisonofanorecticpotenciesofthetrichothecenest2toxinht2toxinandsatratoxingtotheipecacalkaloidemetine AT pestkajamesj comparisonofanorecticpotenciesofthetrichothecenest2toxinht2toxinandsatratoxingtotheipecacalkaloidemetine |