Location: Poisonous Plant Research
Title: Studies on the teratogenicity of anabasine in a rat model Authors
|Hammond, Christian -|
|Hammond, Zachary -|
Submitted to: Toxicon
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 23, 2014
Publication Date: September 1, 2014
Citation: Welch, K.D., Lee, S.T., Panter, K.E., Gardner, D.R., Knoppel, E.L., Green, B.T., Hammond, C.K., Hammond, Z.J., Pfister, J.A. 2014. Studies on the teratogenicity of anabasine in a rat model. Toxicon. 87:32-37. Interpretive Summary: A number of plant toxins have been shown to be teratogenic to livestock. The maternal consumption of plants that contain piperidine, pyridine, or quinolizidine alkaloids has the potential to cause developmental defects in animals. Many of the actions of these alkaloids are mediated by nicotinic acetylcholine receptors (nAChR). In the developing fetus, teratogenic piperidine alkaloid-mediated desensitization of fetal muscle-type nAChR is postulated to inhibit fetal movement, resulting in skeletal flexure defects and cleft palate. There are numerous follow-up studies that need to be conducted to further characterize the teratogenic nature of the individual piperidine, pyridine, and quinolizidine alkaloids. Many of these alkaloids are enantiomers, and characterization of the differences in teratogenicity of the individual enantiomers is also needed. However, many of these alkaloids are present in the plants as a mixture, and some of the alkaloids are not very abundant. Thus it is difficult to obtain sufficient quantities of many of these alkaloids to perform teratology studies in livestock species. Therefore a small rodent model to study the teratogenicity of these alkaloids, including their enantiomers, would be valuable for investigating alkaloids present in only limited quantities. Consequently, 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. However, the data presented in this study suggest that the rat model is not a good model to study the teratogenicity of plant toxins that cause birth defects in livestock by inhibition of nicotinic acetylcholine receptors.
Technical Abstract: 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.