Leighfield Tod A, Muha Noah, Ramsdell John S
Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, NOAA-National Ocean Service , 219 Fort Johnson Road, Charleston, South Carolina 29412, United States.
Chem Res Toxicol. 2014 Jul 21;27(7):1166-75. doi: 10.1021/tx500053f. Epub 2014 Jul 7.
Brevetoxins produced during algal blooms of the dinoflagellate Karenia are metabolized by shellfish into reduction, oxidation, and conjugation products. Brevetoxin metabolites comprising amino acid- and lipid conjugates account for a large proportion of the toxicity associated with the consumption of toxic shellfish. However, the disposition of these brevetoxin metabolites has not been established. Using intravenous exposure to C57BL/6 mice, we investigated the disposition in the body of three radiolabeled brevetoxin metabolites. Amino acid-brevetoxin conjugates represented by S-desoxy-BTX-B2 (cysteine-BTX-B) and lipid-brevetoxin conjugates represented by N-palmitoyl-S-desoxy-BTX-B2 were compared to dihydro-BTX-B. Tissue concentration profiles were unique to each of the brevetoxin metabolites tested, with dihydro-BTX-B being widely distributed to all tissues, S-desoxy-BTX-B2 concentrated in kidney, and N-palmitoyl-S-desoxy-BTX-B2 having the highest concentrations in spleen, liver, and lung. Elimination patterns were also unique: dihydro-BTX-B had a greater fecal versus urinary elimination, whereas urine was a more important elimination route for S-desoxy-BTX-B2, and N-palmitoyl-S-desoxy-BTX-B2 persisted in tissues and was eliminated equally in both urine and feces. The structures particular to each brevetoxin metabolite resulting from the reduction, amino acid conjugation, or fatty acid addition of BTX-B were likely responsible for these tissue-specific distributions and unique elimination patterns. These observed differences provide further insight into the contribution each brevetoxin metabolite class has to the observed potencies.
在腰鞭毛虫卡伦藻藻华期间产生的短裸甲藻毒素会被贝类代谢为还原、氧化和结合产物。由氨基酸和脂质结合物组成的短裸甲藻毒素代谢产物在食用有毒贝类相关的毒性中占很大比例。然而，这些短裸甲藻毒素代谢产物的处置情况尚未明确。通过对C57BL/6小鼠进行静脉注射暴露，我们研究了三种放射性标记的短裸甲藻毒素代谢产物在体内的处置情况。将以S-脱氧-BTX-B2（半胱氨酸-BTX-B）为代表的氨基酸-短裸甲藻毒素结合物和以N-棕榈酰-S-脱氧-BTX-B2为代表的脂质-短裸甲藻毒素结合物与二氢-BTX-B进行了比较。每种测试的短裸甲藻毒素代谢产物的组织浓度分布都各不相同，二氢-BTX-B广泛分布于所有组织，S-脱氧-BTX-B2集中在肾脏，而N-棕榈酰-S-脱氧-BTX-B2在脾脏、肝脏和肺中的浓度最高。消除模式也各不相同：二氢-BTX-B经粪便排泄的比例高于尿液，而尿液是S-脱氧-BTX-B2更重要的排泄途径，N-棕榈酰-S-脱氧-BTX-B2在组织中持续存在，经尿液和粪便的排泄量相当。由BTX-B的还原、氨基酸结合或脂肪酸添加产生的每种短裸甲藻毒素代谢产物特有的结构可能是这些组织特异性分布和独特消除模式的原因。这些观察到的差异为每种短裸甲藻毒素代谢产物类别对观察到的效力的贡献提供了进一步的见解。
