title: Evaluation of developmental toxicity and teratogenicity of diclofenac using Xenopus embryos.
abstract: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and anti-pyretic properties. This compound is therefore used to treat pain, inflammatory disorders, and dysmenorrhea. Due to its multimodal mechanism of action and ability to penetrate placenta, diclofenac is known to have undesirable side effects including teratogenicity. However, limited data exist on its teratogenicity, and a detailed investigation regarding harmful effects of this drug during embryogenesis is warranted. Here, we analyzed the developmental toxic effects of diclofenac using Xenopus embryos according to the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) protocol. Diclofenac treatment exerted a teratogenic effect on Xenopus embryos with a teratogenic index (TI) value of 2.64 TI; if this value is higher than 1.2, the cut-off value indicative of toxicity. In particular, mortality of embryos treated with diclofenac increased in a concentration-dependent manner and a broad spectrum of malformations such as shortening and kinking of the axis, abdominal bulging, and prominent blister formation, was observed. The shape and length of internal organs also differed compared to the control group embryos and show developmental retardation on histological label. However, the expression of major tissue-specific markers did not change when analyzed by reverse transcription-polymerase chain reaction (RT-PCR). In conclusion, diclofenac treatment can promote teratogenicity that results in morphological anomalies, but not disrupt the developmental tissue arrangement during Xenopus embryogenesis.
authors.affiliation: Department of Anatomy, College of Medicine, Kyungpook National University, Daegu 700-422, South Korea.
authors.forename: Jeong-Pil
authors.initials: JP
authors.lastname: Chae
authors.affiliation: Aquaculture Management Division, National Fisheries Research and Development Institute, Busan 619-705, South Korea.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Park
authors.affiliation: Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
authors.forename: Yoo-Seok
authors.initials: YS
authors.lastname: Hwang
authors.affiliation: Aquaculture Management Division, National Fisheries Research and Development Institute, Busan 619-705, South Korea.
authors.forename: Byung-Hwa
authors.initials: BH
authors.lastname: Min
authors.affiliation: Department of Pharmacology, College of Medicine, Kyungpook National University, Daegu 700-422, South Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: ABRC, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, South Korea. Electronic address: leeh@knu.ac.kr.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Anatomy, College of Medicine, Kyungpook National University, Daegu 700-422, South Korea. Electronic address: mjpark@knu.ac.kr.
authors.forename: Mae-Ja
authors.initials: MJ
authors.lastname: Park
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D004008:Diclofenac / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005260:Female; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013723:Teratogens / Q000633:toxicity*; D014981:Xenopus / Q000196:embryology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013723:Teratogens; D004008:Diclofenac
keywords: Diclofenac; Embryotoxicity; FETAX; Teratogenicity; Xenopus laevis