Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice.

Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Research Abstract Details 

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Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Abstract Text:

Ryou Fukushima,Susumu Kanamori,Masahiro Hirashiba,Atsuko Hishikawa,Ri-Ich Muranaka,Masako Kaneto,Kazuichi Nakamura,Ikuo Kato,Ryou Fukushima,Susumu Kanamori,Masahiro Hirashiba,Atsuko Hishikawa,Ri-Ich Muranaka,Masako Kaneto,Kazuichi Nakamura,Ikuo Kato,Ryou Fukushima,Susumu Kanamori,Masahiro Hirashiba,Atsuko Hishikawa,Ri-Ich Muranaka,Masako Kaneto,Kazuichi Nakamura,Ikuo Kato,

Leflunomide is an immunosuppressive agent that inhibits de novo synthesis of pyrimidine nucleotides and the activity of protein tyrosine kinase. This study examined the teratogenicity of Leflunomide in mice. Pregnant mice were treated orally with Leflunomide at a dose of 10, 30 or 70mg/kg/day from day 6 to 15 of pregnancy. At 70mg/kg, all embryos were resorbed and no live fetuses were detected. At 30mg/kg, Leflunomide reduced fetal viability, and increased the incidence of multiple external, skeletal and visceral malformations. Characteristic external malformations were neural tube defects, cleft palate and tail deformities. Limb malformations were observed in a small number of fetuses. Skeletal examinations revealed malformations of cervical to sacral vertebrae, ribs and sternebrae. In the viscerae, the main anomalies were membranous ventricular septum defect and persistent truncus arteriosus. The results of this study indicate that Leflunomide administered at 30mg/kg on days 6 to 15 of pregnancy can induce craniofacial malformations and deformities of the axial skeleton, heart and great vessels in mice.

Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Publishing Authors By Initials

R Fukushima,S Kanamori,M Hirashiba,A Hishikawa,RI Muranaka,M Kaneto,K Nakamura,I Kato,R Fukushima,S Kanamori,M Hirashiba,A Hishikawa,RI Muranaka,M Kaneto,K Nakamura,I Kato,R Fukushima,S Kanamori,M Hirashiba,A Hishikawa,RI Muranaka,M Kaneto,K Nakamura,I Kato,

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Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Reproductive toxicology (Elmsford, N.Y.)

VOLUME: 24

Page Numbers: 310-6

Journal Abbreviation: Reprod. Toxicol.

ISSN: 0890-6238

DAY: 18

MONTH: 05

YEAR: 2007

Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Information

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LANGUAGE: eng

NlmUniqueID: 8803591

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Grant and Affiliation Information for Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice.

AFFILIATION: Drug Safety Evaluation, Developmental Research Laboratories, 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.

Country: United States

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MEDLINETA: Reprod Toxicol

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