Effect of coniine on the developing chick embryo

Abstract

Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.

Piperidine alkaloids: Human and food animal teratogens

“…Coniine (2) is an agonist at fetal muscle-type nAChRs; racemic coniine has an approximate EC 50 of 200 lM in TE-671 cells (Table 1). Coniine (2) ingestion is associated with MCC in livestock species (Panter et al, 1988), but only to a limited extent in rabbits and not in rats (Forsyth and Frank, 1993;Forsyth et al, 1994). Interestingly, two pregnant mares orally dosed gestational days 45-75 with 15.5 mg/kg body weight coniine (2) in the form of dried ground poison hemlock exhibited signs of acute intoxication but their offspring were normal (Keeler et al, 1980).…”

The Avian Embryo: A Developmental Research Tool

“…The substances pass through the shell membrane for absorption by the vitelline plexus underlying the air sac. This method greatly reduces mortality caused by piercing the vitelline membrane and has been used successfully in several teratological experiments by HASHIZUME et al (1992), FORSYTH et al (1994), VORSTER et al (1995 and HEYNS (1997).…”

Effects of Nicotine on Chicken Embryo Development: A Review

“…The remaining two embryos from the groups had significant malformations however, due to the small sample size, a valid determination could not be made regarding nicotine-induced developmental malformations [3]. Forsyth et al [26] also observed mortality in nicotine-treated embryos in a dose-dependent manner with 1%, 5%, and 10% nicotine sulfate solutions producing a mortality rate of 37%, 67%, and 100%, respectively. Exposure of embryos at 48h incubation to 1 mg of nicotine caused a high incidence of embryonic death [27].…”

“…Nicotine is also a known stimulant on cholinoceptors which produces a depolarization blockage in skeletal muscles and ultimately causes paralysis [30]. Forsyth et al [26] observed embryonic movements for a 5-minute interval, one hour after nicotine administration, and found no movement in the treated embryos. Hamamichi and Nishigori [30] also observed complete stoppage, possibly paralytic, of swing-like movements in embryos treated with 10μg of nicotine and 1 x ACSE (aqueous cigarette smoke extract).…”