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

Xiaoyu Ji,Mengbi Yang,Zhong Zuo,Ka Hang Or,Wan Sze Yim

doi:10.3390/toxins11060353

Xiaoyu Ji, Mengbi Yang + Show 3 more

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https://doi.org/10.3390/toxins11060353

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Journal: Toxins	Publication Date: Jun 18, 2019
Citations: 18	License type: CC BY 4.0

Affiliation: Chinese University of Hong Kong

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.

Highlights

The processed lateral root of Radix Aconiti Lateralis is known as Fuzi, an extensively used traditional Chinese medicine in China and other Asian countries [1]
[27], 5% ammonium methanol used method, we found the response of targeted alkaloids were not high enough for detection, due to to elute compounds binding on the mode cation-exchange (MCX) cartridge
Our current study revealed the remarkably high tendency of the toxic alkaloids to distribute into the liver after oral ingestion of Fuzi at a clinically relevant dosing regimen, which could partially explain the hepatotoxicity reported in previously conducted studies

Summary

Introduction

The processed lateral root of Radix Aconiti Lateralis is known as Fuzi, an extensively used traditional Chinese medicine in China and other Asian countries [1]. Among the 500 well-known traditional Chinese medicine (TCM) formulae used in clinics, approximately. 13.2% include Fuzi [1]. Fuzi-containing prescriptions are usually given orally, with 81.8% of them used at 5 g/person/day, 9.1% of them used at 10 g/person/day and the rest used at. Fuzi has promising therapeutic effects, aconitum poisoning has been extensively given 17 orally, with of them during used at 51990–99, g/person/day, 9.1% ofform them Hong used at Kong. 10 g/person/day and reported with cases from Taiwan. 39 cases during 2012–19, the rest used at g/person/day [3].

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