Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Reprod Toxicol. 2011 Jul;32(1):129-37. doi: 10.1016/j.reprotox.2011.05.015. Epub 2011 Jun 6.
Albendazole (ABZ) is used as an anthelmintic drug in humans and animals. ABZ has been shown to cause developmental toxicity in experimental animals, however it is not clear if this is caused by the parent compound or a metabolite. Zebrafish embryos were exposed from 1 to 144hpf (hours post fertilization) to investigate the developmental toxicity of ABZ, the first metabolite albendazole sulphoxide and the subsequent metabolites albendazole sulphone (ABZSO(2)) and albendazole-2-aminosulphone (ABZSO(2)NH(2)). The results showed that ABZ caused malformations of head and tail and embryonic lethality from 0.3μM. In contrast, the metabolites did not display developmental toxicity at any tested concentration. Dechorionation did not influence the developmental toxic potential of ABZ and ABZSO, indicating that bioavailability was not a limiting factor. Chemical analysis showed that at sublethal concentrations, most of ABZ was metabolized to ABZSO. The results demonstrate that in zebrafish embryos ABZ rather than ABZSO displays developmental toxicity.
阿苯达唑（ABZ）被用作人类和动物的驱虫药物。ABZ 已被证明在实验动物中具有发育毒性，但尚不清楚这是母体化合物还是代谢物引起的。从受精后 1 至 144 小时（hpf）暴露于斑马鱼胚胎中，以研究 ABZ、第一个代谢物阿苯达唑亚砜以及随后的代谢物阿苯达唑砜（ABZSO(2)）和阿苯达唑-2-氨基砜（ABZSO(2)NH(2)) 的发育毒性。结果表明，ABZ 从 0.3μM 开始引起头部和尾部畸形和胚胎致死。相比之下，在任何测试浓度下，代谢物均未显示出发育毒性。去壳化并未影响 ABZ 和 ABZSO 的发育毒性潜力，表明生物利用度不是限制因素。化学分析表明，在亚致死浓度下，ABZ 大部分代谢为 ABZSO。结果表明，在斑马鱼胚胎中，ABZ 而不是 ABZSO 表现出发育毒性。
