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Effect of Cys, GSH, and pH on Mercury Release from Tibetan Medicine Zuotai, β-HgS, and α-HgS in Artificial Gastrointestinal Juices

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Abstract

Zuotai, also named as “gTso thal”, a known Tibetan medicinal mixture containing insoluble cubic crystal mercuric sulfide (β-HgS), has been used to treat diseases with long history. The mercury release ratio from Zuotai in gastrointestinal environment is one determinant factor for its bioavailability and biological effect. However, the information is still scarce now. Therefore, the study was designed to investigate the effect of sulfhydryl biomolecules [l-cysteine (Cys) and glutathione (GSH)] and pH on mercury dissociation from Zuotai, β-HgS, and hexagonal crystal mercuric sulfide (α-HgS) in artificial gastrointestinal juices or pure water with a 1:100 solid-liquid ratio. And, the digestion and peristalsis of gastrointestinal tract were simulated in vitro. The results showed the following trend for the mercury release ratio of Zuotai, artificial gastric juice > artificial intestinal juice > pure water, whereas the trend for β-HgS and α-HgS was as follows, artificial intestinal fluid > artificial gastric fluid > pure water. The mercury release ratios of Zuotai, β-HgS, and α-HgS significantly increased in artificial intestinal juice containing l-Cys or GSH compared to those without sulfhydryl biomolecules in the juice. However, in contrast to the results observed for β-HgS and α-HgS, the mercury release ratio of Zuotai was reduced remarkably in pure water and artificial gastric juice with Cys or GSH. And, we found that strong acidic or strong alkaline environments promoted the dissociation of mercury from Zuotai, β-HgS, and α-HgS. Taken together, current findings may contribute to other studies regarding clinical safety and bioavailability of the traditional drug Zuotai containing β-HgS.

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Abbreviations

HgS:

Mercuric sulfide

Cys:

l-cysteine

GSH:

Glutathione

LD0 or MTD:

Lethal dose 0% or maximal tolerance dose

LD50 :

Median lethal dose

K sp :

Solubility product constant

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Acknowledgments

Yuzhi Du (Professor), Hongxia Yang (PhD), Lujing Geng (PhD), and Hongtao Bi (PhD) of Northwest Institute of Plateau Biology, Chinese Academy of Sciences, are acknowledged for their assistance in measurements and data analysis.

Funding

This work was supported by “The Dawn of West China” 2014 Talent Training Program of Chinese Academy of Sciences (Y529021211), the Science Foundation for Young Scholars of Qinghai Province (2016-ZJ-919Q), the National Natural Science Foundation of China (81374063), and the Development Program of Key Laboratory in Qinghai Province (2017-ZJ-Y08).

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Authors and Affiliations

  1. Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xinning Road 23, Xining, Qinghai, 810008, China

    Zhiyuan Zheng, Ming Zhang, Yuancan Xiao, Lixin Wei & Cen Li

  2. University of Chinese Academy of Sciences, Beijing, 100047, China

    Zhiyuan Zheng & Ming Zhang

  3. Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences, Xining, Qinghai, 810008, China

    Yuancan Xiao, Lixin Wei & Cen Li

Authors
  1. Zhiyuan Zheng
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  2. Ming Zhang
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  3. Yuancan Xiao
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  4. Lixin Wei
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  5. Cen Li
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Contributions

Zhiyuan Zheng (zhengzhiyuan12@mails.ucas.ac.cn) and Ming Zhang (zhangming13@mails.ucas.ac.cn) performed the main experiments with equal contribution to this work, and are joint first authors. Yuancan Xiao (ycxiao@nwipb.cas.cn) performed auxiliary implementation of experiments. Lixin Wei (lxwei@nwipb.cas.cn) and Cen Li (licen@nwipb.cas.cn) contributed equally to the experiment design and the composition of this manuscript.

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Correspondence to Lixin Wei or Cen Li.

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The authors declare that they have no conflicts of interest.

Raw data 1: Mercury leaching ratio (μg/g) from Tibetan medicine Zuotai, β-HgS, and α-HgS in pure water and artificial gastrointestinal juices containing Cys (or GSH) or not. https://figshare.com/s/ff2314be1b9ab2ecf3b4

Raw data 2: Leaching ratio (μg/g) of mercury from Tibetan medicine Zuotai, β-HgS, and α-HgS in different pH solutions. https://figshare.com/s/3cab66153bdd9b4a4609

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Zheng, Z., Zhang, M., Xiao, Y. et al. Effect of Cys, GSH, and pH on Mercury Release from Tibetan Medicine Zuotai, β-HgS, and α-HgS in Artificial Gastrointestinal Juices. Biol Trace Elem Res 184, 536–545 (2018). https://doi.org/10.1007/s12011-017-1185-x

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