Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice
Open Access
- 24 June 2021
- journal article
- Published by F1000 Research Ltd in F1000Research
- Vol. 10, 203
- https://doi.org/10.12688/f1000research.40667.2
Abstract
Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.Funding Information
- National Natural Science Foundation of China (81560592, 82060817)
- Chinese Academy of Sciences (2017-ZJ-Y08)
This publication has 35 references indexed in Scilit:
- Potency of Individual Bile Acids to Regulate Bile Acid Synthesis and Transport Genes in Primary Human Hepatocyte CulturesToxicological Sciences, 2014
- Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57Bl/6 mouse heartToxicology Letters, 2014
- Besondere Qualitätsaspekte von Tibetischen Arzneimitteln - Erkenntnisse aus über 40 Jahren Erfahrung in der Herstellung in der SchweizComplementary Medicine Research, 2013
- Mercury modulates the cytochrome P450 1a1, 1a2 and 1b1 in C57BL/6J mice: in vivo and in vitro studiesToxicology and Applied Pharmacology, 2013
- Tibetan Medicine: A Systematic Review of the Clinical Research Available in the WestEvidence-Based Complementary and Alternative Medicine, 2013
- Coordinated Regulation of Hepatic Phase I and II Drug-Metabolizing Genes and Transporters using AhR-, CAR-, PXR-, PPARα-, and Nrf2-Null MiceDrug Metabolism and Disposition, 2012
- Evaluation of hepatotoxicity potential of cinnabar-containing An-Gong-Niu-Huang Wan, a patent traditional Chinese medicineRegulatory Toxicology and Pharmacology, 2011
- Regulation of CYP1A1 by heavy metals and consequences for drug metabolismExpert Opinion on Drug Metabolism & Toxicology, 2009
- Can Homeopathically Prepared Mercury Cause Symptoms in Healthy Volunteers? A Randomized, Double-Blind Placebo-Controlled TrialThe Journal of Alternative and Complementary Medicine, 2001
- Bioactivation of Halogenated Hydrocarbons by Cytochrome P4502E1Critical Reviews in Toxicology, 1993