Gross congenital abnormalities induced by leflunomide in mice embryos

Abstract

Leflunomide is an antirheumatic drug commonly used by females, as this disease is common in females and there are chances of pregnancy while taking this medication in initial months of pregnancy this commonly prescribed drug lacks studies related to its teratogenic potential. Present study was conducted to know about its teratogenicity in mice embryos. Pregnant mice were exposed to Leflunomide by oral route on gestational days 6 to 11 either as single dose in one of the gestational days or continuous doses. The embryos were collected on day 19 of gestation, were measured and examined for external anomalies. Findings suggested that Leflunomide was embryo lethal when given as continuous dose as there were 100% resorption of embryos. In the single dose group, maximum resorptions were found when was given in early pregnancy. Other anomalies included malrotated limbs, open eyes, kinking of tails, defect in anterior abdominal wall and visceroptosis and anencephaly. these anomalies were noted in embryos exposed to leflunomide only on gestational days 7 and 8. The above findings suggest that leflunomide interferes with embryonic growth It also interferes with neural tube closure leading to anencephaly. Findings of open eyes and kinking tails suggest that the drug may affect epithelial and mesodermal growth. Leflunomide perhaps interferes with the lateral folding of the embryo leading to defect in the anterior abdominal wall and visceroptosis. The present study concludes that Leflunomide is teratogenic and embryolethal in mice and should be avoided in human pregnancy.