Teratogenicity in swine of the tobacco alkaloid anabasine isolated from Nicotiana glauca.
Nicotiana glauca, wild tree tobacco, induces arthrogrypotic congenital defects in piglets similar to those induced by Nicotiana tabacum, common tobacco. The present work was conducted to isolate the principal alkaloid of N. glauca, anabasine, in large quantity and good purity and to test the teratogenicity of the compound in pigs. The isolated compound was established to be anabasine and to be of suitable purity by chemical characterization. It proved to be teratogenic. Typical arthrogrypotic defects were induced in 21 of 26 offspring (three of three litters) when dams ingested 2.6 mg of the compound per kg body weight twice daily during the 43rd-53rd days of gestation. Of three dams dosed with 1.66 g/kg/day of the dried plant material during the 43rd-53rd days, one delivered deformed offspring representing one-third of all offspring in that group. These arthrogrypotic defects induced by anabasine were indistinguishable clinically from defects induced by either N. glauca or N. tabacum. In addition, anabasine at a dose of 2.6 mg/kg twice daily or N. glauca plant material at 1.66 gm/kg daily induced cleft palate in over three-fourths of offspring (100% of litters) when dams ingested either during the 30th-37th days of gestation or during longer periods that included those days.
D000014:Abnormalities, Drug-Induced; D000691:Anabasine / Q000302:isolation & purification / Q000633:toxicity*; D000818:Animals; D001176:Arthrogryposis / Q000139:chemically induced*; D002849:Chromatography, Gas; D005260:Female; D005865:Gestational Age; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010880:Piperidines / Q000633:toxicity*; D010947:Plants, Toxic; D011247:Pregnancy; D013552:Swine; D014026:Nicotiana / Q000032:analysis
D010880:Piperidines; D000691:Anabasine