Berry John P, Gibbs Patrick D L, Schmale Michael C, Saker Martin L
Department of Chemistry and Biochemistry, 354 Marine Science Building, Florida International University, 3000 NE 151st Street, North Miami, FL 33181, USA.
Toxicon. 2009 Feb;53(2):289-99. doi: 10.1016/j.toxicon.2008.11.016. Epub 2008 Dec 6.
Cyanobacteria produce a diverse array of toxic or otherwise bioactive compounds that pose growing threats to human and environmental health. We utilized the zebrafish (Danio rerio) embryo, as a model of vertebrate development, to investigate the inhibition of development pathways (i.e. developmental toxicity) by the cyanobacterial toxin, cylindrospermopsin (CYN), as well as extracts from various isolates of Cylindrospermopsis raciborskii and Aphanizomenon ovalisporum. CYN was toxic only when injected directly into embryos, but not by direct immersion at doses up to 50mug/ml. Despite the dose dependency of toxicity observed following injection of CYN, no consistent patterns of developmental defects were observed, suggesting that toxic effects of CYN may not target specific developmental pathways. In contrast, direct immersion of embryos in all of the extracts resulted in both increased mortality and reproducible, consistent, developmental dysfunctions. Interestingly, there was no correlation of developmental toxicity observed for these extracts with the presence of CYN or with previously reported toxicity for these strains. These results suggest that CYN is lethal to zebrafish embryos, but apparently inhibits no specific developmental pathways, whereas other apparent metabolites from C. raciborskii and A. ovalisporum seem to reproducibly inhibit development in the zebrafish model. Continued investigation of these apparent, unknown metabolites is needed.
蓝藻会产生各种各样的有毒或具有其他生物活性的化合物，这些化合物对人类和环境健康构成了日益严重的威胁。我们利用斑马鱼（Danio rerio）胚胎作为脊椎动物发育的模型，来研究蓝藻毒素柱孢藻毒素（CYN）以及来自柱孢鱼腥藻（Cylindrospermopsis raciborskii）和卵形鱼腥藻（Aphanizomenon ovalisporum）各种分离株的提取物对发育途径的抑制作用（即发育毒性）。CYN只有直接注射到胚胎中时才具有毒性，而在高达50μg/ml的剂量下直接浸泡则没有毒性。尽管注射CYN后观察到毒性具有剂量依赖性，但未观察到一致的发育缺陷模式，这表明CYN的毒性作用可能不会针对特定的发育途径。相比之下，将胚胎直接浸泡在所有提取物中均导致死亡率增加以及可重复、一致的发育功能障碍。有趣的是，这些提取物的发育毒性与CYN的存在或这些菌株先前报道的毒性没有相关性。这些结果表明，CYN对斑马鱼胚胎具有致死性，但显然不会抑制特定的发育途径，而来自柱孢鱼腥藻和卵形鱼腥藻的其他明显代谢产物似乎在斑马鱼模型中可重复地抑制发育。需要对这些明显的未知代谢产物继续进行研究。
