Sandvik Morten, Miles Christopher O, Wilkins Alistair L, Fæste Christiane
Norwegian Veterinary Institute, P. O. Box 750 Sentrum, NO-0106, Oslo, Norway.
Biotoxin Metrology, Measurement Science and Standards, National Research Council, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada.
Toxicon X. 2020 Mar 23;6:100031. doi: 10.1016/j.toxcx.2020.100031. eCollection 2020 Jun.
We have investigated the metabolism of pectenotoxin-2 (PTX-2) using primary hepatocytes from Wistar rats in suspension. Purified PTX-2 was rapidly metabolized. Two major and several minor oxidized PTX-2 metabolites were formed, none of which had retention times corresponding to PTX-1, -11, or -13. Hydrolysis products, such as PTX-2 seco acid, were not observed. Preliminary multi-stage LC-MS analyses indicated that the major hepatic PTX-2 metabolites resulted from the insertion of an oxygen atom at the positions C-19 to C-24, or at C-44. The rapid oxidative metabolism may explain the low oral toxicity of PTXs observed in vivo studies.
我们使用Wistar大鼠的原代悬浮肝细胞研究了pectenotoxin-2（PTX-2）的代谢。纯化的PTX-2迅速代谢。形成了两种主要的和几种次要的氧化PTX-2代谢产物，其中没有一种的保留时间与PTX-1、-11或-13相对应。未观察到水解产物，如PTX-2开环酸。初步的多级液相色谱-质谱分析表明，主要的肝脏PTX-2代谢产物是由于在C-19至C-24位或C-44位插入了一个氧原子。快速的氧化代谢可能解释了体内研究中观察到的PTXs口服毒性较低的现象。
