| Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. | |
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MedLine Citation:
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PMID: 17604599 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 70 mg/kg/day from day 6 to 15 of pregnancy. At 70 mg/kg, all embryos were resorbed and no live fetuses were detected. At 30 mg/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 30 mg/kg on days 6 to 15 of pregnancy can induce craniofacial malformations and deformities of the axial skeleton, heart and great vessels in mice. |
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Authors:
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Ryou Fukushima; Susumu Kanamori; Masahiro Hirashiba; Atsuko Hishikawa; Ri-Ich Muranaka; Masako Kaneto; Kazuichi Nakamura; Ikuo Kato |
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Publication Detail:
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Type: Journal Article Date: 2007-05-18 |
Journal Detail:
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Title: Reproductive toxicology (Elmsford, N.Y.) Volume: 24 ISSN: 0890-6238 ISO Abbreviation: Reprod. Toxicol. Publication Date: 2007 Nov-Dec |
Date Detail:
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Created Date: 2007-11-05 Completed Date: 2008-01-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8803591 Medline TA: Reprod Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 310-6 Citation Subset: IM |
Affiliation:
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Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan. ryou.fukushima@shionogi.co.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Drug-Induced* Adjuvants, Immunologic / toxicity* Administration, Oral Animals Aorta / abnormalities, drug effects Bone and Bones / abnormalities, drug effects Craniofacial Abnormalities / chemically induced, embryology Dose-Response Relationship, Drug Embryo Loss Female Fetal Resorption Heart Defects, Congenital / chemically induced, embryology Isoxazoles / toxicity* Male Mice Pregnancy Teratogens / classification, toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 0/Isoxazoles; 0/Teratogens; 75706-12-6/leflunomide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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