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Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis)

While iron overload disorder (IOD) and related disease states are not considered a common occurrence in domestic equids, these issues appear prevalent in black rhinoceroses under human care. In addressing IOD in black rhinos, altering dietary iron absorption and excretion may be the most globally pr...

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Autores principales: Sullivan, Kathleen E., Lavin, Shana R., Livingston, Shannon, Knutson, Mitchell, Valdes, Eduardo V., Warren, Lori K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542505/
https://www.ncbi.nlm.nih.gov/pubmed/35894091
http://dx.doi.org/10.1111/jpn.13745
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author Sullivan, Kathleen E.
Lavin, Shana R.
Livingston, Shannon
Knutson, Mitchell
Valdes, Eduardo V.
Warren, Lori K.
author_facet Sullivan, Kathleen E.
Lavin, Shana R.
Livingston, Shannon
Knutson, Mitchell
Valdes, Eduardo V.
Warren, Lori K.
author_sort Sullivan, Kathleen E.
collection PubMed
description While iron overload disorder (IOD) and related disease states are not considered a common occurrence in domestic equids, these issues appear prevalent in black rhinoceroses under human care. In addressing IOD in black rhinos, altering dietary iron absorption and excretion may be the most globally practical approach. A main option for treatment used across other species such as humans, is chelation therapy using iron‐specific synthetic compounds. As horses may serve as an appropriate digestive model for the endangered rhinoceros, we evaluated the potential use of the oral iron chelator N,N‐bis(2‐hydroxybenzyl)ethylenediamine‐N,N‐diacetic acid (HBED) in horses for safety and efficacy prior to testing in black rhinoceros. Health and iron digestibility and dynamics were assessed in horses (n = 6) before, and after treatment with HBED (50 mg/kg body weight) for 8 days using a crossover design with serum, faecal and urine collection. A preliminary pharmacokinetic trial was also performed but no trace of HBED was found in serially sampled plasma through 8 h post‐oral dosing. HBED increased urinary iron output in horses compared to control by 0.7% of total iron intake (p < 0.01), for an average of 27 mg urinary iron/day, similar to human chelation goals. Blood chemistry, blood cell counts and overall wellness were not affected by treatment. As healthy horses are able to regulate iron absorption, the lack of change in iron balance is unsurprising. Short‐term HBED administration appeared to be safely tolerated by horses, therefore it was anticipated it would also be safe to administer to black rhinos for the management of iron overload.
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spelling pubmed-95425052022-10-14 Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis) Sullivan, Kathleen E. Lavin, Shana R. Livingston, Shannon Knutson, Mitchell Valdes, Eduardo V. Warren, Lori K. J Anim Physiol Anim Nutr (Berl) Original Articles While iron overload disorder (IOD) and related disease states are not considered a common occurrence in domestic equids, these issues appear prevalent in black rhinoceroses under human care. In addressing IOD in black rhinos, altering dietary iron absorption and excretion may be the most globally practical approach. A main option for treatment used across other species such as humans, is chelation therapy using iron‐specific synthetic compounds. As horses may serve as an appropriate digestive model for the endangered rhinoceros, we evaluated the potential use of the oral iron chelator N,N‐bis(2‐hydroxybenzyl)ethylenediamine‐N,N‐diacetic acid (HBED) in horses for safety and efficacy prior to testing in black rhinoceros. Health and iron digestibility and dynamics were assessed in horses (n = 6) before, and after treatment with HBED (50 mg/kg body weight) for 8 days using a crossover design with serum, faecal and urine collection. A preliminary pharmacokinetic trial was also performed but no trace of HBED was found in serially sampled plasma through 8 h post‐oral dosing. HBED increased urinary iron output in horses compared to control by 0.7% of total iron intake (p < 0.01), for an average of 27 mg urinary iron/day, similar to human chelation goals. Blood chemistry, blood cell counts and overall wellness were not affected by treatment. As healthy horses are able to regulate iron absorption, the lack of change in iron balance is unsurprising. Short‐term HBED administration appeared to be safely tolerated by horses, therefore it was anticipated it would also be safe to administer to black rhinos for the management of iron overload. John Wiley and Sons Inc. 2022-07-27 2022-09 /pmc/articles/PMC9542505/ /pubmed/35894091 http://dx.doi.org/10.1111/jpn.13745 Text en © 2022 The Authors. Journal of Animal Physiology and Animal Nutrition published by Wiley‐VCH GmbH. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Sullivan, Kathleen E.
Lavin, Shana R.
Livingston, Shannon
Knutson, Mitchell
Valdes, Eduardo V.
Warren, Lori K.
Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis)
title Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis)
title_full Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis)
title_fullStr Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis)
title_full_unstemmed Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis)
title_short Safety and efficacy of a novel iron chelator (HBED; (N,N′‐Di(2‐hydroxybenzyl)ethylenediamine‐N,N′‐diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis)
title_sort safety and efficacy of a novel iron chelator (hbed; (n,n′‐di(2‐hydroxybenzyl)ethylenediamine‐n,n′‐diacetic acid)) in equine (equus caballus) as a model for black rhinoceros (diceros bicornis)
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542505/
https://www.ncbi.nlm.nih.gov/pubmed/35894091
http://dx.doi.org/10.1111/jpn.13745
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