The effect of intermittent dosing of Nicotiana glauca on teratogenesis in goats

Authors: Welch, Kevin; Panter, Kip; Lee, Stephen; Gardner, Dale

Submitted to: Toxicon
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/20/2014
Publication Date: 1/2/2015
Publication URL: http://handle.nal.usda.gov/10113/62783
Citation: Welch, K.D., Panter, K.E., Lee, S.T., Gardner, D.R. 2015. The effect of intermittent dosing of Nicotiana glauca on teratogenesis in goats. Toxicon. 93:119-124.

Interpretive Summary: Lupines are responsible for a condition in cattle referred to as “crooked calf syndrome” that occurs when pregnant cattle graze lupines containing the quinolizidine alkaloid anagyrine, or the piperidine alkaloids ammodendrine, N-methyl-ammodendrine or N-acetyl hystrine. Similar malformations are also seen in animals poisoned by Conium, containing the alkaloids coniine, '-coniceine, and N-methylconiine, and Nicotiana species, containing the alkaloid anabasine, with a similar mechanism of action. A goat model using Nicotiana glauca has been established to study the mechanism of action of lupine-induced cleft palate and crooked calf syndrome. One potential management strategy to minimize lupine-induced birth defects could include utilizing an intermittent grazing schedule to allow short durations of grazing in lupine-infested areas followed by movement to a lupine-free pasture. The anticipated outcome of using an intermittent grazing schedule would be such that the sustained inhibition of fetal movement would not occur. Our hypothesis is that intermittent periods of normal movement will allow the fetus to develop normally within the sensitive developmental period. The objective of this study was to use a goat model to determine if an intermittent schedule of five continuous days on treatment followed by two days off treatment would be sufficient to decrease, or prevent, the incidence of anabasine-induced malformations. The data from this study confirms that in goats, Nicotiana glauca (anabasine) is a potent teratogen. This study also confirms that there is an inverse relationship between the amount of serum anabasine in the dam and the extent of fetal movement. The results from this study, however, indicate that an intermittent grazing program of five days exposure with two days of non-exposure is insufficient to prevent significant malformations from occurring in goats. However, we still feel that an intermittent grazing program could be a viable management option to limit lupine-type malformations. Therefore, future studies will be conducted to determine how long of a rest period (off treatment) is required to provide the fetus with a sufficient duration of normal movement to prevent severe malformations from occurring. Future studies will also evaluate the practicality of an intermittent dosing regimen in other livestock species and with other plants, especially lupine-induced malformations in cattle.

Technical Abstract: Sustained inhibition of fetal movement in livestock species, induced by several poisonous plants, can result in numerous skeletal-contracture malformations. Lupines are responsible for a condition in cattle referred to as “crooked calf syndrome” that occurs when pregnant cattle graze teratogenic lupines. Similar malformations are also seen in animals poisoned by Conium (coniine) and Nicotiana (anabasine) species. A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to use a goat model to determine if an intermittent schedule of five continuous days on treatment followed by two days off treatment would be sufficient to decrease, or prevent, the incidence of anabasine-induced malformations. The data from this study suggest that, for Nicotiana glauca in goats, the intermittent grazing program of five days exposure with two days of non-exposure is insufficient to prevent significant skeletal malformations from occurring. However, this study did demonstrate an inverse relationship between the amount of serum anabasine in the dam and the extent of fetal movement.