Improvement of the evaluation method for teratogenicity using zebrafish embryos

Abstract

ABSTRACTcially for evaluation of the teratogenicity, due to their small size, rapid development, transparency, and maintain them in culture plates, evaluate the teratogenicity in short term, conduct morphological assessment of each organ without any autopsy operation. The purpose of the present study was to improve an evaluation method for the teratogenicity of test compounds with high throughput ability and prediction -were exposed to test compounds from 5-6 to 144 hr post-fertilization, (hpf) corresponding to the organogenesis period. Morphological changes or functional abnormalities induced by test compound treatments were assessed and scored at 11 endpoints, and the potential of teratogenicity was judged based on the score. As a validation assay of the system, the potentials of 59 known teratogenic or non-teratogenic test -rectly predicted in 90% (53/59) of all compounds with low false negative and false positive rates. These valuable tool for early stage screening in drug discovery.

Comparative study of the zebrafish embryonic toxicity test and mouse embryonic stem cell test to screen developmental toxicity of human pharmaceutical drugs

“…In other reports, the accuracies of the ZET (87% and 90%) (Brannen et al, 2010;Yamashita et al, 2014) and mEST (78% and 100%) (Genschow et al, 2002;Riebeling et al, 2015) were higher than those in our study. The reason for the lower accuracy in our assay system is unclear.…”

“…Thus, we evaluated the compounds at 100 μM in the ZET as the highest concentration. The highest concentration in a ZET by Yamashita et al (2014) was 1,000 μM. Although the set of chemical compounds is not same in our assay system, they showed higher sensitivity (88%).…”

“…Although the set of chemical compounds is not same in our assay system, they showed higher sensitivity (88%). Furthermore, both we and Yamashita et al (2014) used the same seven compounds (dexamethasone, diclofenac, indomethacin, methotrexate, penicillin G, retinoic acid, and ribavirin), and the results were the same without indomethacin. Additionally, we evaluated hydroxyurea at 10 mM and thalidomide at 1 mM, but they did not cause any morphological changes in the ZET (data not shown).…”

Using zebrafish in systems toxicology for developmental toxicity testing

“…VPA and topiramate have been shown to cause a hypomorphic lower jaw (Yamashita et al. ; Inoue et al. ).…”

“…In humans, anti-epileptic drugs taken during pregnancy can increase the risk of congenital jaw malformation (Koo and Zavras 2013). VPA and topiramate have been shown to cause a hypomorphic lower jaw (Yamashita et al 2014;Inoue et al 2015). Many anti-epileptic drugs can also inhibit histone deacetylase (HDAC) (Eyal et al 2004); the protein HDAC1 regulates neural crest-derived craniofacial development (Ignatius et al 2013).…”