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Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats

Although Radix Aconiti Lateralis (Fuzi) is an extensively used traditional Chinese medicine with promising therapeutic effects and relatively well-reported toxicities, the related toxic aconitum alkaloid concentrations in major organs after its short-term and long-term intake during clinical practic...

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Autores principales: Ji, Xiaoyu, Yang, Mengbi, Or, Ka Hang, Yim, Wan Sze, Zuo, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628749/
https://www.ncbi.nlm.nih.gov/pubmed/31216736
http://dx.doi.org/10.3390/toxins11060353
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author Ji, Xiaoyu
Yang, Mengbi
Or, Ka Hang
Yim, Wan Sze
Zuo, Zhong
author_facet Ji, Xiaoyu
Yang, Mengbi
Or, Ka Hang
Yim, Wan Sze
Zuo, Zhong
author_sort Ji, Xiaoyu
collection PubMed
description Although Radix Aconiti Lateralis (Fuzi) is an extensively used traditional Chinese medicine with promising therapeutic effects and relatively well-reported toxicities, the related toxic aconitum alkaloid concentrations in major organs after its short-term and long-term intake during clinical practice are still not known. To give a comprehensive understanding of Fuzi-induced toxicities, current study is proposed aiming to investigate the biodistribution of the six toxic alkaloids in Fuzi, namely Aconitine (AC), Hypaconitine (HA), Mesaconitine (MA), Benzoylaconine (BAC), Benzoylhypaconine (BHA) and Benzoylmesaconine (BMA), after its oral administrations at clinically relevant dosing regimen. A ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for simultaneous quantification of six toxic alkaloids in plasma, urine and major organs of Sprague Dawley rats after oral administrations of two commonly used Fuzi preparations, namely Heishunpian and Paofupian, at their clinically relevant dose for single and 15-days. Among the studied toxic alkaloids and organs, BMA demonstrated the highest concentrations in all studied organs with liver containing the highest amount of the studied alkaloids, indicating their potential hepatotoxicity. Moreover, tissue accumulation of toxic alkaloids after multiple dose was observed, suggesting the needs for dose adjustment and more attention to the toxicities induced by chronic use of Fuzi in patients.
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spelling pubmed-66287492019-08-05 Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats Ji, Xiaoyu Yang, Mengbi Or, Ka Hang Yim, Wan Sze Zuo, Zhong Toxins (Basel) Article Although Radix Aconiti Lateralis (Fuzi) is an extensively used traditional Chinese medicine with promising therapeutic effects and relatively well-reported toxicities, the related toxic aconitum alkaloid concentrations in major organs after its short-term and long-term intake during clinical practice are still not known. To give a comprehensive understanding of Fuzi-induced toxicities, current study is proposed aiming to investigate the biodistribution of the six toxic alkaloids in Fuzi, namely Aconitine (AC), Hypaconitine (HA), Mesaconitine (MA), Benzoylaconine (BAC), Benzoylhypaconine (BHA) and Benzoylmesaconine (BMA), after its oral administrations at clinically relevant dosing regimen. A ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for simultaneous quantification of six toxic alkaloids in plasma, urine and major organs of Sprague Dawley rats after oral administrations of two commonly used Fuzi preparations, namely Heishunpian and Paofupian, at their clinically relevant dose for single and 15-days. Among the studied toxic alkaloids and organs, BMA demonstrated the highest concentrations in all studied organs with liver containing the highest amount of the studied alkaloids, indicating their potential hepatotoxicity. Moreover, tissue accumulation of toxic alkaloids after multiple dose was observed, suggesting the needs for dose adjustment and more attention to the toxicities induced by chronic use of Fuzi in patients. MDPI 2019-06-18 /pmc/articles/PMC6628749/ /pubmed/31216736 http://dx.doi.org/10.3390/toxins11060353 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ji, Xiaoyu
Yang, Mengbi
Or, Ka Hang
Yim, Wan Sze
Zuo, Zhong
Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats
title Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats
title_full Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats
title_fullStr Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats
title_full_unstemmed Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats
title_short Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats
title_sort tissue accumulations of toxic aconitum alkaloids after short-term and long-term oral administrations of clinically used radix aconiti lateralis preparations in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628749/
https://www.ncbi.nlm.nih.gov/pubmed/31216736
http://dx.doi.org/10.3390/toxins11060353
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