Study of Aconitine toxicity in rat embryos in vitro

BACKGROUND: Aconitum is widely used in traditional medicine for its anti-inflammatory, analgesic, and cardiotonic properties. Knowledge is limited, however, on its effects on embryonic development. METHODS: Whole embryo culture was applied to explore the effects of aconitine on rat embryos during their critical period of organogenesis. All embryos isolated on gestational day 9.5 were exposed to 0, 1, 2.5, 5, and 10µg/ml of aconitine with and without S9 mix, and scored for their growth and differentiation at the end of the 48-hr culture period. RESULTS: The embryonic growth and development were adversely affected at the concentration of 2.5µg/ml aconitine without S9 mix, represented as reduced crown-rump length and head length, decreased number of somites, and lower morphologic score. When the concentration of aconitine was increased to 5µg/ml, it induced severe dysmorphogenesis effects, including cardiac defect (undivided cardiac tube and inflated pericardial cavity), irregular somites, and brain malformation (e.g., narrow brain vesicles). In the presence of S9 mix, Aconitine toxicity to rat embryos was reduced to a certain extent. CONCLUSIONS: Our study showed that Aconitine had direct embryotoxic effects during the rat organogenetic period. NOAEL was about 1µg/ml and metabolism in S9 mix could induce the attenuation of Aconitine toxicity. Until more is known about the effects of Aconitine in pregnant women, we suggest its use should be treated with caution. Birth Defects Res B, 2007.