Toxicity of bryostatin‐1 on the embryo‐fetal development of Sprague‐Dawley rats

BACKGROUND: Bryostatin-1, a highly oxygenated marine macrolide with a unique polyacetate backbone isolated from the marine animal Bugula neritina (Linnaeus), is now being developed as an anti-cancer drug for treating malignancy. In the present study, developmental toxicity of bryostatin-1 was evaluated in Sprague–Dawley rats. METHODS: Bryostatin-1 was intravenously administered to rats on gestation days 6–15 at 4.0, 8.0, and 16.0 µg/kg on a daily basis. Then the reproductive parameters were determined in animals, and fetuses were examined for external, visceral, and skeletal malformations. RESULTS: The total weight gains were significantly different in animals between the control group and 8.0 and 16.0 µg/kg bryostatin-1 groups during and after treatment. The resorption and death fetus rates were significantly different between the bryostatin-1 group (16 µg/kg) and the control group. The fetal weight and fetal crown-rump length in the bryostatin-1 groups were significantly lower than that in the control group. CONCLUSIONS: Our results indicated that maternal toxicity occurred when the dose of bryostatin-1 was at 8.0 µg/kg, embryotoxicity at 16.0 µg/kg, and fetotoxicity at 4.0 µg/kg; but bryostatin-1 showed no teratogenic effect in rats. In light of our findings, bryostatin-1 should be used with caution in pregnant women with cancer, if they would like to continue the pregnancy. Birth Defects Res (Part B) 89:171–174, 2010. © 2010 Wiley-Liss, Inc.