Abraham Ann, Plakas Steven M, Wang Zhihong, Jester Edward L E, El Said Kathleen R, Granade Hudson R, Henry Michael S, Blum Patricia C, Pierce Richard H, Dickey Robert W
Gulf Coast Seafood Laboratory, US Food and Drug Administration, P.O. Box 158, 1 Iberville Drive, Dauphin Island, AL 36528-0158, USA.
Toxicon. 2006 Jul;48(1):104-15. doi: 10.1016/j.toxicon.2006.04.015. Epub 2006 May 6.
Several novel brevetoxin derivatives were isolated and identified in Karenia brevis cultures and natural blooms by using solid phase extraction (SPE) and LC/MS(MS) techniques. These analogs were more polar compared with previously described brevetoxins, and were poorly extractable by conventional non-polar solvent (chloroform) partitioning. Brevetoxin analogs were structurally confirmed as hydrolyzed (open A-ring) forms of brevetoxins PbTx-1, PbTx-7, PbTx-2, and PbTx-3, and of oxidized PbTx-1 and PbTx-2. Some of these open A-ring derivatives were in greater abundance than their non-hydrolyzed counterparts. All were in much greater abundance in bloom water filtrate compared with cell-rich fractions. Open A-ring compounds were cytotoxic in mouse neuroblastoma (N2a) cell assay. In the K. brevis bloom-exposed Eastern oyster, brevetoxin metabolites with opened A rings were identified (e.g., open-ring cysteine-PbTx conjugates), contributing to their overall toxin burden.
通过使用固相萃取（SPE）和液相色谱/质谱（MS）技术，在短裸甲藻培养物和自然水华中分离并鉴定出了几种新型短裸甲藻毒素衍生物。与先前描述的短裸甲藻毒素相比，这些类似物极性更强，难以通过传统的非极性溶剂（氯仿）分配法进行提取。短裸甲藻毒素类似物在结构上被确认为短裸甲藻毒素PbTx-1、PbTx-7、PbTx-2和PbTx-3以及氧化的PbTx-1和PbTx-2的水解（开环A环）形式。其中一些开环A环衍生物的丰度高于其未水解的对应物。与富含细胞的部分相比，所有这些物质在水华滤液中的丰度都要高得多。开环A环化合物在小鼠神经母细胞瘤（N2a）细胞试验中具有细胞毒性。在暴露于短裸甲藻水华的东部牡蛎中，鉴定出了具有开环A环的短裸甲藻毒素代谢物（例如，开环半胱氨酸-PbTx缀合物），这增加了它们的总体毒素负担。
