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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

1
School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR, China
2
School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Toxins 2019, 11(6), 353; https://doi.org/10.3390/toxins11060353
Received: 31 May 2019 / Revised: 13 June 2019 / Accepted: 14 June 2019 / Published: 18 June 2019
(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)
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Abstract

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. View Full-Text
Keywords: Radix Aconiti Lateralis preparations; short-term and long-term usage; di-ester diterpenoid alkaloids; mono-ester diterpenoid alkaloids; biodistribution Radix Aconiti Lateralis preparations; short-term and long-term usage; di-ester diterpenoid alkaloids; mono-ester diterpenoid alkaloids; biodistribution
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Ji, X.; Yang, M.; Or, K.H.; Yim, W.S.; Zuo, Z. Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats. Toxins 2019, 11, 353.

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