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Biochem Biophys Res Commun. 2018 Jun 22;501(2):329-335. doi: 10.1016/j.bbrc.2018.03.002. Epub 2018 Mar 2.

Evaluation of the toxic effects of celecoxib on Xenopus embryo development.

Author information

1
Department of Anatomy, Kyungpook National University, Daegu 41944, South Korea.
2
Pediatrics, Kyungpook National University, Daegu 41944, South Korea.
3
Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu 41944, South Korea.
4
Molecular Medicine, Kyungpook National University, Daegu 41944, South Korea.
5
Department of Surgery, Uijeongbu St. Mary's Hospital, The Catholic University of Korea #271, Cheonbo-ro, Uijeongbu-City, Gyenggi-Do 480-717, South Korea.
6
General Surgery, School of Medicine, Kyungpook National University, Daegu 41944, South Korea.
7
School of Life Science, Kyungpook National University, Daegu 41944, South Korea.
8
Department of Anatomy, Kyungpook National University, Daegu 41944, South Korea. Electronic address: mjpark@knu.ac.kr.

Abstract

Celecoxib is a non-steroidal anti-inflammatory drug that selectively inhibits cyclooxygenase-2 and is prescribed for severe pain and inflammation. The excellent therapeutic effects of celecoxib mean that it is frequently used clinically, including for women of child-bearing age. However, the prenatal effects of this compound have not been studied extensively in vertebrates. The present study examined the developmental toxicity of celecoxib using a frog embryo teratogenic assay-Xenopus (FETAX). In addition, we examined its effects on cell migration using co-cultures of human umbilical vein endothelial cells and 10T1/2 cells. These studies revealed that celecoxib induced concentration-dependent mortality and various malformations of the Xenopus internal organs, including gut miscoiling, haemorrhage, and oedema. Celecoxib also downregulated the expression of vascular wall markers (Msr and alpha smooth muscle actin) and other organ-specific markers (Nkx2.5, Cyl104 and IFABP). In vitro co-culture studies revealed that celecoxib inhibited pericyte migration and differentiation into vascular smooth muscle cells. In conclusion, celecoxib was both toxic and teratogenic in Xenopus embryos, where it produced serious heart and vessel malformation by inhibiting vascular wall maturation and vascular network formation.

KEYWORDS:

Celecoxib; FETAX; Teratogenicity; Vessel formation; Xenopus laevis

PMID:
29505793
DOI:
10.1016/j.bbrc.2018.03.002
[Indexed for MEDLINE]

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