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Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs

Our previous studies have investigated the systematic pharmacokinetic characteristics, biological activities, and toxicity of arctigenin. In this research, the potential toxicities of arctigenin in beagle dogs were investigated via repeated 28-day subcutaneous injections. Beagle dogs were randomly d...

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Autores principales: Li, Jie, Lv, Yun-gang, Pan, Li-hong, Yao, Fang-fang, Peng, Tao, Tan, Yu-jun, Zhang, Gui-Min, Liu, Zhong, Yao, Jing-chun, Ren, Yu-shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807677/
https://www.ncbi.nlm.nih.gov/pubmed/31680982
http://dx.doi.org/10.3389/fphar.2019.01218
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author Li, Jie
Lv, Yun-gang
Pan, Li-hong
Yao, Fang-fang
Peng, Tao
Tan, Yu-jun
Zhang, Gui-Min
Liu, Zhong
Yao, Jing-chun
Ren, Yu-shan
author_facet Li, Jie
Lv, Yun-gang
Pan, Li-hong
Yao, Fang-fang
Peng, Tao
Tan, Yu-jun
Zhang, Gui-Min
Liu, Zhong
Yao, Jing-chun
Ren, Yu-shan
author_sort Li, Jie
collection PubMed
description Our previous studies have investigated the systematic pharmacokinetic characteristics, biological activities, and toxicity of arctigenin. In this research, the potential toxicities of arctigenin in beagle dogs were investigated via repeated 28-day subcutaneous injections. Beagle dogs were randomly divided into control, vehicle [polyethylene glycol (PEG)], and arctigenin 6, 20, 60 mg/kg treated groups. The whole experimental period lasted 77 days, including adaptive period (35 days), drug exposure period (animals were treated with saline, PEG, or arctigenin for 28 consecutive days), and recovery period (14 days). Arctigenin injection (60 mg/kg) affected the lymphatic hematopoietic, digestive, urinary, and cardiovascular systems, and all the impact on these tissues resulted in death in five dogs (three female and two male dogs); 20 mg/kg arctigenin injection resulted in toxic reactions of the lymphatic hematopoietic and digestive systems; and 6 mg/kg arctigenin and PEG injection did not lead to significant toxic reactions. Meanwhile, there were no sexual differences of drug exposure and accumulation when dogs underwent different dosages. As stated previously, the toxic target organs of arctigenin administration include lymphatic hematopoietic, digestive (liver and gallbladder), urinary (kidney), and cardiovascular (heart) systems, and the no observed adverse effect level (NOAEL) of arctigenin is less than 6 mg/kg.
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spelling pubmed-68076772019-11-01 Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs Li, Jie Lv, Yun-gang Pan, Li-hong Yao, Fang-fang Peng, Tao Tan, Yu-jun Zhang, Gui-Min Liu, Zhong Yao, Jing-chun Ren, Yu-shan Front Pharmacol Pharmacology Our previous studies have investigated the systematic pharmacokinetic characteristics, biological activities, and toxicity of arctigenin. In this research, the potential toxicities of arctigenin in beagle dogs were investigated via repeated 28-day subcutaneous injections. Beagle dogs were randomly divided into control, vehicle [polyethylene glycol (PEG)], and arctigenin 6, 20, 60 mg/kg treated groups. The whole experimental period lasted 77 days, including adaptive period (35 days), drug exposure period (animals were treated with saline, PEG, or arctigenin for 28 consecutive days), and recovery period (14 days). Arctigenin injection (60 mg/kg) affected the lymphatic hematopoietic, digestive, urinary, and cardiovascular systems, and all the impact on these tissues resulted in death in five dogs (three female and two male dogs); 20 mg/kg arctigenin injection resulted in toxic reactions of the lymphatic hematopoietic and digestive systems; and 6 mg/kg arctigenin and PEG injection did not lead to significant toxic reactions. Meanwhile, there were no sexual differences of drug exposure and accumulation when dogs underwent different dosages. As stated previously, the toxic target organs of arctigenin administration include lymphatic hematopoietic, digestive (liver and gallbladder), urinary (kidney), and cardiovascular (heart) systems, and the no observed adverse effect level (NOAEL) of arctigenin is less than 6 mg/kg. Frontiers Media S.A. 2019-10-16 /pmc/articles/PMC6807677/ /pubmed/31680982 http://dx.doi.org/10.3389/fphar.2019.01218 Text en Copyright © 2019 Li, Lv, Pan, Yao, Peng, Tan, Zhang, Liu, Yao and Ren http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Jie
Lv, Yun-gang
Pan, Li-hong
Yao, Fang-fang
Peng, Tao
Tan, Yu-jun
Zhang, Gui-Min
Liu, Zhong
Yao, Jing-chun
Ren, Yu-shan
Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs
title Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs
title_full Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs
title_fullStr Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs
title_full_unstemmed Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs
title_short Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs
title_sort toxicity study of 28-day subcutaneous injection of arctigenin in beagle dogs
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807677/
https://www.ncbi.nlm.nih.gov/pubmed/31680982
http://dx.doi.org/10.3389/fphar.2019.01218
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