Studies on the teratogenicity of anabasine in a rat model

A number of plant toxins have been shown to be teratogenic to livestock. The teratogenic action of some of these alkaloids is mediated by nicotinic acetylcholine receptors (nAChR). However, for many of these alkaloids it is difficult to obtain sufficient quantities of individual alkaloids to perform teratology studies in cattle, sheep or goats. Therefore the objective of this study was to determine if a rat model can be utilized to study and characterize the teratogenic nature of individual plant toxins that are nAChR agonists. In this study, we evaluated the teratogenicity of anabasine from tree tobacco, by feeding pregnant rats rodent chow that contained 0, 50, 125, 250, 500, or 1000 µg of anabasine / g of chow from gestational day (GD) 6-21. Chow consumption and animal body weight were measured every two days from GD6 through GD21. Fetal movement was evaluated via ultrasonography in several of the dams from the control and 500 µg/g groups, with fetal movement observed in all of the dams. On GD21 the dams were euthanized by CO2 asphyxiation and the gravid uteri were removed by cesarean section. The gravid uteri and individual pups were weighed. The number of implantation sites and resorptions was recorded. The pups were evaluated for bone malformations including cleft palate and scoliosis. The results of this study indicate that anabasine does not induce cleft palate formation in rats. Additionally, there was no difference in the number of dams that had pups with scoliosis in the treated groups compared to the control group. It is possible that in the rat model, anabasine administered orally via the chow does not result in sufficient reduction in fetal movement to cause significant malformations such as cleft palate. Overall, the data from this study suggest that the rat is not a good model to study the teratogenicity of plant toxins that are nAChR agonists.