title: Embryonic exposure to diclofenac disturbs actin organization and leads to myofibril misalignment.
abstract: The objective of this study was to investigate the embryotoxicity of diclofenac. Zebrafish (Danio rerio) embryos at 12 hpf were treated with different dosages of diclofenac (0-2,000 ppm) for different time courses (12-72 hr). Results showed no evident differences in survival rates or morphological changes between the mock-treated control (0 ppm) zebrafish embryos and those with 1-ppm diclofenac-exposure (12-24, 12-36 hpf). In contrast, after higher doses (5 and 10 ppm) of exposure, embryos displayed some defective phenotypes, including malformed somite boundary, a twisted body axis, and shorter body length. In addition, diclofenac-treated embryos exhibited significantly reduced frequencies of spontaneous in-chorion contractions in comparison with mock-control littermates (mock-control: 13.20 ± 2.24 vs. 5-10 ppm diclofenac: 6.66 ± 1.35-3.03 ± 1.84). Subtle changes were easily observed by staining with specific monoclonal antibodies F59 and phalloidin to detect morphological changes in muscle fibers and formation of F-actin, respectively. Our data show that diclofenac treatment disturbs actin organization and muscle fiber alignment, thus causing malformed somite phenotypes.
authors.affiliation: Institute of Medical Sciences, Buddhist Tzu Chi University, Hualien, Taiwan.
authors.forename: Ying-Hsin
authors.initials: YH
authors.lastname: Chen
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Chang
authors.forename: Yun-Hsin
authors.initials: YH
authors.lastname: Wang
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Wen
authors.forename: Yun-Chen
authors.initials: YC
authors.lastname: Chen
authors.forename: Sheng-Chuan
authors.initials: SC
authors.lastname: Hu
authors.forename: Dah-Shyong
authors.initials: DS
authors.lastname: Yu
authors.forename: Yau-Hung
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D004008:Diclofenac / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D016014:Linear Models; D016015:Logistic Models; D009210:Myofibrils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D019170:Somites / Q000187:drug effects / Q000473:pathology; D015027:Zebrafish / Q000002:abnormalities / Q000196:embryology*
chemical_list: D000199:Actins; D004008:Diclofenac