Hilborn E D, Carmichael W W, Soares R M, Yuan M, Servaites J C, Barton H A, Azevedo S M F O
United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina, USA.
Environ Toxicol. 2007 Oct;22(5):459-63. doi: 10.1002/tox.20281.
Microcystins are among the most commonly detected toxins associated with cyanobacteria blooms worldwide. Two episodes of intravenous microcystin exposures occurred among kidney dialysis patients during 1996 and 2001. Analysis of serum samples collected during these episodes suggests that microcystins are detectable as free and bound forms in human serum. Our goal was to characterize the biochemical evidence for human exposure to microcystins, to identify uncertainties associated with interpretation of these observed results, and to identify research needs. We analyzed serum samples using enzyme-linked immunosorbent assay (ELISA) methods to detect free microcystins, and gas chromatography/mass spectrometry (GC/MS) to detect 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB). MMPB is derived from both free and protein-bound microcystins by chemical oxidation, and it appears to represent total microcystins present in serum. We found evidence of free microcystins in patient serum for more than 50 days after the last documented exposure. Serum concentrations of free microcystins were consistently lower than MMPB quantification of total microcystins: free microcystins as measured by ELISA were only 8-51% of total microcystin concentrations as detected by the GC/MS method. After intravenous exposure episodes, we found evidence of microcystins in human serum in free and protein-bound forms, though the nature of the protein-bound forms is uncertain. Free microcystins appear to be a small but variable subset of total microcystins present in human serum. Research is needed to elucidate the human toxicokinetics of microcystins, in part to determine how observed serum concentrations can be used to estimate previous microcystin exposure.
微囊藻毒素是全球范围内与蓝藻水华相关的最常检测到的毒素之一。1996年至2001年期间，肾透析患者中发生了两起静脉内接触微囊藻毒素的事件。对这些事件期间采集的血清样本进行分析表明，微囊藻毒素在人血清中可检测为游离和结合形式。我们的目标是描述人类接触微囊藻毒素的生化证据，识别与这些观察结果解释相关的不确定性，并确定研究需求。我们使用酶联免疫吸附测定（ELISA）方法分析血清样本以检测游离微囊藻毒素，并用气相色谱/质谱（GC/MS）检测2-甲基-3-甲氧基-4-苯基丁酸（MMPB）。MMPB通过化学氧化从游离和蛋白质结合的微囊藻毒素中衍生而来，它似乎代表血清中存在的总微囊藻毒素。我们发现，在最后一次记录的接触后50多天，患者血清中存在游离微囊藻毒素的证据。游离微囊藻毒素的血清浓度始终低于总微囊藻毒素的MMPB定量：ELISA测定的游离微囊藻毒素仅为GC/MS方法检测的总微囊藻毒素浓度的8-51％。静脉内接触事件后，我们发现人血清中存在游离和蛋白质结合形式的微囊藻毒素的证据，尽管蛋白质结合形式的性质尚不确定。游离微囊藻毒素似乎是人类血清中总微囊藻毒素的一个小但可变的子集。需要开展研究以阐明微囊藻毒素的人体毒代动力学，部分目的是确定如何利用观察到的血清浓度来估计先前的微囊藻毒素接触情况。
