Study of Aconitine toxicity in rat embryos in vitro

Xiao, Kai; Wang, Li; Liu, Yuqing; Peng, Cheng; Yan, Guangyan; Zhang, Jianjun; Zhuo, Yanqiang

doi:10.1002/bdrb.20116

Cited by 25 publications

(15 citation statements)

References 18 publications

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“…No publications were found to show that this interesting bioactivity has been properly studied as yet. Until more is known, practitioners should be rigorously cautious in administering to pregnant women, since a recent study showed that AC had direct embryo-toxic effects in rats during the organogenetic period (Xiao et al, 2007).…”

Section: Therapy Of Abdominal Colic and Irregular Menstruationmentioning

confidence: 99%

Aconitum in Traditional Chinese Medicine—A valuable drug or an unpredictable risk?

Singhuber

Zhu

Prinz

et al. 2009

Journal of Ethnopharmacology

409

277

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Section: Therapy Of Abdominal Colic and Irregular Menstruationmentioning

confidence: 99%

Aconitum in Traditional Chinese Medicine—A valuable drug or an unpredictable risk?

Singhuber

Zhu

Prinz

et al. 2009

Journal of Ethnopharmacology

409

277

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“…As far as we know, the toxicity of exposure is mainly related to neurological, cardiovascular and gastrointestinal systems, [24][25][26] and sometimes embryotoxicity. 27 The damage to hepatocytes and nephrocytes caused by aconitum alkaloids cannot, however, be ignored, particularly when it is combined with other herbs and/or chemical drugs. Transporters as a superfamily of proteins, which act as barriers to xenobiotics crossing the cell membrane, are critical for the fate of chemicals in vivo, including the pharmacokinetic pattern, safety and efficacy.…”

Section: Discussionmentioning

confidence: 99%

Identification of key transporters mediating uptake of aconitum alkaloids into the liver and kidneys and the potential mechanism of detoxification by active ingredients of liquorice

Wang

et al. 2019

RSC Adv.

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Aconite as a commonly used herb has been extensively applied in the treatment of rheumatoid arthritis, as pain relief, as well as for its cardiotonic actions. Aconitum alkaloids have been shown to be the most potent ingredients in aconite, in terms of efficacy against disease, but they are also highly toxic. Apart from neurological and cardiovascular toxicity exposed, the damage to hepatocytes and nephrocytes with long-term use of aconitum alkaloids should also be carefully considered. This study attempted to investigate the critical role of uptake transporters mediating the transport of aconitum alkaloids into the liver and the kidneys. The resulting data revealed that hOATP1B1, 1B3, hOCT1 and hOAT3 were mainly involved in the uptake of aconitum alkaloids. Additionally, the inhibitory effects of bioactive ingredients of liquorice on uptake transporters were screened and further confirmed by determining the IC 50 values.The in vitro study suggested that liquorice might lower the toxicity of aconite by reducing its exposure in the liver and/or kidneys through inhibition of uptake transporters. Eventually, the in vivo study was indicative of detoxification of liquorice by decreasing the exposure of aconitine as representative compound in liver after co-administration, even though the exposure in kidney altered was less significant. In summary, hOATP1B1, 1B3, hOCT1 and hOCT3 were determined as the key uptake transporters mediating the transport process of aconitum alkaloids into the liver and/or kidneys, and liquorice may alleviate the toxicity caused by reduction of exposure through inhibition of those key uptake transporters.

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“…As methods of evaluating drug safety continue to improve, they have included experiments during the teratogenic sensitivity period, in vitro whole embryo culture and other methods, all of which can be used to evaluate the safety of CM (Han et al, 2014). Xiao et al used whole embryo culture to explore the effects of aconitine on rat embryos during their critical period of organogenesis and found that a concentration of 5 μg ml −1 of aconitine could induce severe dysmorphogenesis, including cardiac defects (undivided cardiac tube and inflated pericardial cavity), irregular somites and brain malformation (e.g., narrow brain vesicles) (Xiao et al, 2007). Whole embryo culture in rats revealed that the essential oil of Curcuma zedoaria produced a concentration-dependent toxicity ex vivo in the embryos, and led to weight loss as well as abnormal haematological and biochemical effects on pregnant females and their embryos (Zhou et al, 2013).…”

Section: Chinese Medicines For Pregnancymentioning

confidence: 99%

Metabolomics of the amniotic fluid: Is it a feasible approach to evaluate the safety of Chinese medicine during pregnancy?

Shan

Xie

Zhou

et al. 2018

J of Applied Toxicology

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The use of Chinese medicines (CMs) during pregnancy has long been a major public health concern. Although CMs have been shown to be effective in treating infertility and preventing miscarriage, their use has been restricted, mainly because of limited knowledge of their potential toxicity. Accurate toxicology data are urgently required to assess whether these CMs are safe for maternal health and fetal development. Amniotic fluid (AF) contains carbohydrates, lipids and phospholipids, urea and proteins, all of which aid in the growth of the fetus and reflect the mother's health status as well. The changes in metabolomic patterns of AF are related to pathophysiological occurrences during the course of pregnancy. In this review, we provide a summary of the research performed in recent years on metabolomic AF samples, and use our previous study as an example to explore the feasibility of metabolomics of AF to evaluate the safety of CMs during pregnancy. We believe that metabolomics of AF play a far more important role than traditional morphology methods in the safety evaluation of CMs for pregnancy, with a higher sensitivity and correlation.

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Study of Aconitine toxicity in rat embryos in vitro

Cited by 25 publications

References 18 publications

Aconitum in Traditional Chinese Medicine—A valuable drug or an unpredictable risk?

Aconitum in Traditional Chinese Medicine—A valuable drug or an unpredictable risk?

Identification of key transporters mediating uptake of aconitum alkaloids into the liver and kidneys and the potential mechanism of detoxification by active ingredients of liquorice

Metabolomics of the amniotic fluid: Is it a feasible approach to evaluate the safety of Chinese medicine during pregnancy?

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