The Role of Clomipramine in Potentiating the Teratogenic Effects of Caffeine in Pregnant Rats: A Histopathological Study

Since little is known about the teratogenic effects of clomipramineused concurrently with caffeineduring the organogenesisperiod, the aim of this study was to test the teratogenic effects of a coadministration of caffeineand clomipramineon rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control) received 0.5 mL of normal saline. Clomipraminewas injected at 40 mg/kg and 80 mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeinein doses of 60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of 40 mg/kg clomipramineand 60 mg/kg caffeine, and the seventh group was given clomipramineand caffeineat 80 mg/kg and 120 mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeineor combinations of caffeineand clomipramineshowed a significant rate of cleft palatedevelopment, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (). This study concludes that caffeinein high doses or the simultaneous administration of caffeineand clomipramineleads to teratogenicity.