Evaluation of in vitro embryotoxicity tests for Chinese herbal medicines

Lu Li; Ling Yin Tang; Bo Liang; Rongyun Wang; Qiuhua Sun; Clara Bik San Lau; Ping Chung Leung; Ellen Fritsche; Manfred Liebsch; Andrea E M Seiler Wulczyn; Horst Spielmann; Chi Chiu Wang

doi:10.1016/j.reprotox.2019.06.001

Evaluation of in vitro embryotoxicity tests for Chinese herbal medicines

Reprod Toxicol. 2019 Oct:89:45-53. doi: 10.1016/j.reprotox.2019.06.001. Epub 2019 Jun 20.

Authors

Affiliations

¹ College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong; Institute of Chinese Medicine & State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, Hong Kong.
² Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong.
³ School of Nursing, Zhejiang Chinese Medical University, Hangzhou, China.
⁴ Institute of Chinese Medicine & State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, Hong Kong.
⁵ IUF-Leibniz Research Institute of Environmental Medicine, Düsseldorf, Germany.
⁶ Central Ethics Committee for Stem Cell Research (ZES), Robert Koch Institute, Berlin, Germany.
⁷ Institute for Pharmacy, Faculty of Biology, Chemistry, and Pharmacy, Freie Universität, Berlin, Germany.
⁸ College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong; School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: [email protected].

PMID: 31228572
DOI: 10.1016/j.reprotox.2019.06.001

Abstract

Chinese herbal medicines (CHMs) have been widely used during pregnancy, but feto-embryo safety tests are lacking. Here we evaluated in vitro embryotoxicity tests (IVTs) as alternative methods in assessing developmental toxicity of CHMs. Ten CHMs were selected and classified as strongly, weakly and non-embryotoxic. Three well validated IVTs and prediction models (PMs), including embryonic stem cell test (EST), micromass (MM) and whole embryo culture (WEC), were compared. All strongly embryotoxic CHMs were predicted by MM and WEC PM2. While all weakly embryotoxic CHMs were predicted by MM and WEC PM1. All non-embryotoxic CHMs were classified by EST, MM, but over-classified as weakly embryotoxic by WEC PM1. Overall predictivity, precision and accuracy of WEC determined by PM2 were better than EST and MM tests. Compared with validated chemicals, performance of IVTs for CHMs was comparable. So IVTs are adequate to identify and exclude embryotoxic potential of CHMs in this training set.

Keywords: Chinese medicines; Embryotoxicity; In vitro tests; Pregnancy; Safety.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blastocyst Inner Cell Mass / drug effects
Blastocyst Inner Cell Mass / metabolism
Blastocyst Inner Cell Mass / pathology
Cell Differentiation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drugs, Chinese Herbal / classification
Drugs, Chinese Herbal / toxicity*
Embryo, Mammalian / drug effects*
Embryo, Mammalian / metabolism
Embryo, Mammalian / pathology
Embryonic Development / drug effects
Embryonic Stem Cells / drug effects*
Embryonic Stem Cells / metabolism
Embryonic Stem Cells / pathology
In Vitro Techniques
Mice, Inbred ICR
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / pathology
Predictive Value of Tests
Rats, Sprague-Dawley
Sensitivity and Specificity
Teratogens / classification
Teratogens / toxicity*
Toxicity Tests / methods*

Substances

Drugs, Chinese Herbal
Teratogens