title: [Toxic effects of trimethadione on zebrafish early development].
abstract: To further understand the neural toxicity and teratogenicity of antiepileptic drugs in clinic, we established a zebrafish model for antiepileptic toxicity using trimethadione as a probe drug. The results indicated that embryonic malformation occurred under trimethadione treatment in a concentration-dependent manner. The defects included growth retardation, small head, eyes and acoustic capsule, deficient semicircular canals and otolith, and abnormal cardiovascular system. The number of hair cells in neuromast ML2 was obviously reduced in the treated larvae. Whole mount in situ hybridization indicated that the gene expression patterns of brain marker genes, such as zic1 and xb51, and autophagic gene atg5 was changed significantly. The result of RT-PCR showed that the expressions of hearing genes val and hmx2 were also changed in the trimethadione-treated embryos. All these findings suggest that brain tissue and the neural sensors for body balance and hearing are the main targets of trimethadione toxicity, and that zebrafish is able to mimic mammal responses to the teratogenicity and the neural toxicity of trimethadione in the embryonic and larva development.
authors.affiliation: Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. yd06413qw@126.com
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.forename: Zhan-Ying
authors.initials: ZY
authors.lastname: Hu
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Tong
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.forename: Xue-Fu
authors.initials: XF
authors.lastname: You
authors.forename: Jing-Pu
authors.initials: JP
authors.lastname: Zhang
mesh_terms: D000015:Abnormalities, Multiple / Q000139:chemically induced; D000818:Animals; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*; D014293:Trimethadione / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D013723:Teratogens; D014293:Trimethadione