Biooxidation of Ciguatoxins Leads to Species-Specific Toxin Profiles.

Biooxidation of Ciguatoxins Leads to Species-Specific Toxin Profiles.
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DOI:
10.3390/toxins9070205
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发表时间:
2017-06-29
期刊:
影响因子:
4.2
通讯作者:
Yasumoto T
Yasumoto T
中科院分区:
医学2区
文献类型:
--
作者:
Ikehara T;Kuniyoshi K;Oshiro N;Yasumoto T

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雪卡毒素(CTX)污染全世界的鱼类,并导致食源性疾病雪卡毒素。在太平洋,这些毒素是由甲藻Gambierdiscus toxicus产生的,它通过食物链在鱼体内积累,并经过氧化修饰,产生许多类似物。在这项研究中,我们使用参考毒素用液相色谱-串联质谱(LC-MS/MS)分析检测了CTX的体外氧化,发现由鱼产生的CTX 4A,CTX 4 B和CTX 3C被氧化为鱼类中发现的类似物,即CTX 1B,52-epi-54-deoxyCTX 1B,54-deoxyCTX 1B,2-hydroxyCTX 3C和2,3-dihydroxyCTX 3C。该氧化由人CYP 3A 4、鱼肝S9组分和从代表性的食蟹鱼类(Lutjanus bohar,L. monostigumus和点石鲷Oplegnathus punctatus)。此外,从非ciguateric鱼(L. gibbus和L.在体外,冲绳的fulviflamma)也将CTX 4A和CTX 4 B转化为CTX 1B、54-脱氧CTX 1B和52-表-54-脱氧CTX 1B。这是第一项证明这些毒素的酶促氧化的研究,并提供了深入了解物种特异性毒素谱发展的机制以及这些毒素在人类和鱼类中的命运。
Ciguatoxins (CTXs) contaminate fish worldwide and cause the foodborne illness ciguatera. In the Pacific, these toxins are produced by the dinoflagellate Gambierdiscus toxicus, which accumulates in fish through the food chain and undergoes oxidative modification, giving rise to numerous analogs. In this study, we examined the oxidation of CTXs in vitro with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using reference toxins, and found that CTX4A, CTX4B, and CTX3C, which are produced by the alga, are oxidized to the analogs found in fish, namely CTX1B, 52-epi-54-deoxyCTX1B, 54-deoxyCTX1B, 2-hydroxyCTX3C, and 2,3-dihydroxyCTX3C. This oxidation was catalyzed by human CYP3A4, fish liver S9 fractions, and microsomal fractions prepared from representative ciguateric fishes (Lutjanus bohar, L. monostigumus, and Oplegnathus punctatus). In addition, fish liver S9 fractions prepared from non-ciguateric fishes (L. gibbus and L. fulviflamma) in Okinawa also converted CTX4A and CTX4B to CTX1B, 54-deoxyCTX1B, and 52-epi-54-deoxyCTX1B in vitro. This is the first study to demonstrate the enzymatic oxidation of these toxins, and provides insight into the mechanism underlying the development of species-specific toxin profiles and the fate of these toxins in humans and fish.
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