Plasma protein binding of tetrodotoxin in the marine puffer fish Takifugu rubripes

Plasma protein binding of tetrodotoxin in the marine puffer fish Takifugu rubripes
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DOI:
10.1016/j.toxicon.2009.09.006
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发表时间:
2010-02-01
期刊:
影响因子:
2.8
通讯作者:
Nagashima, Yuji
Nagashima, Yuji
中科院分区:
医学4区
文献类型:
--
作者:
Matsumoto, Takuya;Tanuma, Daisuke;Nagashima, Yuji

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为了阐明河豚毒素(TTX)在河豚鱼体内的分布与血浆蛋白结合的关系,我们采用平衡透析法测定了红鳍东方鲀(Takifugu rubripes)和无毒的大泷黄颡鱼(Hrammos otakii)血浆以及牛血清白蛋白(BSA)和牛α 1-酸性糖蛋白(AGP)溶液中TTX的蛋白结合。TTX(100-1000 μ g/mL)以非饱和方式以低亲和力与红足锥虫血浆中的蛋白质结合。结合TTX的量随TTX浓度线性增加,在1000 μ g TTX/mL时达到3.92 +/- 0.42 μ g TTX/mg蛋白。红足赤霉血浆中约80%的TTX在所检测的TTX浓度范围内未结合,表明TTX在广泛的TrX浓度范围内主要以未结合形式存在于红足赤霉循环血液中。TTX也与H. otakii血浆蛋白、BSA和牛AGP。血中TTX结合量与H.在1000 μ gTTX/ml时,otakii和BSA中的TTX/mg蛋白分别为1.86 ± 0.36和4.65 ± 0.70 μ gTTX/mg蛋白,在200 μ gTTX/mL时,牛AGP中的TTX/mg蛋白为8.78 ± 0.25 μ gTTX/mg蛋白。(C)2009爱思唯尔有限公司版权所有。
To elucidate the involvement of plasma protein binding in the disposition of tetrodotoxin (TTX) in puffer fish, we used equilibrium dialysis to measure protein binding of TTX in the plasma of the marine puffer fish Takifugu rubripes and the non-toxic greenling Hexagrammos otakii, and in solutions of bovine serum albumin (BSA) and bovine alpha-1-acid glycoprotein (AGP). TTX (100-1000 mu g/mL) bound to protein in T rubripes plasma with low affinity in a non-saturable manner. The amount of bound TTX increased linearly with the TTX concentration, reaching 3.92 +/- 0.42 mu g TTX/mg protein at 1000 mu g TTX/mL. Approximately 80% of the TTX in the plasma of T rubripes was unbound in the concentration range of TTX examined, indicating that TTX exists predominantly in the unbound form in the circulating blood of T rubripes at a wide range of TrX concentrations. TTX also bound non-specifically to H. otakii plasma proteins, BSA, and bovine AGP. The amount of the bound TTX in the plasma of H. otakii and BSA, respectively, was 1.86 +/- 0.36 and 4.65 +/- 0.70 mu g TTX/mg protein at 1000 mu gTTX/ml, and that in the bovine AGP was 8.78 +/- 0.25 mu gTTX/mg protein at 200 mu gTTX/mL. (C) 2009 Elsevier Ltd. All rights reserved.