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 microg/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 microg/kg bryostatin-1 groups during and after treatment. The resorption and death fetus rates were significantly different between the bryostatin-1 group (16 microg/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 microg/kg, embryotoxicity at 16.0 microg/kg, and fetotoxicity at 4.0 microg/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.
Jiangbo
Zhu
Z
Department of Toxicology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, PR China.
Xuying
Wan
W
Yuping
Zhu
Z
Xili
Ma
M
Yiwen
Zheng
Z
Tianbao
Zhang
Z
D000818:Animals; D054713:Bryostatins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity; D018675:Toxicity Tests
D054713:Bryostatins; D013723:Teratogens; C046785:bryostatin 1