Prelusky D B, Hartin K E, Trenholm H L
Animal Research Centre, Agriculture Canada Ottawa, Ontario.
J Environ Sci Health B. 1990 Jun;25(3):395-413. doi: 10.1080/03601239009372697.
Deoxynivalenol (DON) is one of the major mycotoxins produced by Fusarium fungi. In evaluating DON as a potent CNS (emetic, anorexic) agent, its cerebral spinal fluid (CSF) and plasma pharmacokinetics were studied in pigs, a species very sensitive to the effects of DON, and sheep, a more tolerant animal. After intravenous administration, DON was detected very rapidly (less than 2.5 min) in the CSF of both species, but whereas peak levels (t-max) occurred at 5-10 min in sheep, in swine it was 30-60 min. It would appear that the very rapid and extensive tissue distribution of DON in swine (Vd gamma = 1.13 1 kg-1) may be slowing the rate of diffusion of the toxin into the CSF compared to sheep (Vd beta = 0.19 1 kg-1) where the toxin is confined essentially to the extracellular compartment. Area under curve calculations indicate approximately 2 1/2 times the amount of toxin eventually reaches the pig CSF compared to sheep CSF. A good relationship between blood-CSF DON levels was apparent in both species, although limitations in detection methods made it impossible to resolve a slow terminal phase (gamma) in swine CSF which was evident in the plasma profile after iv administration. Following oral administration of DON to pigs, a close correlation between plasma and CSF DON levels was observed. The toxin could be detected in CSF for up to 20 hr post-dosing.
脱氧雪腐镰刀菌烯醇（DON）是镰刀菌产生的主要霉菌毒素之一。在评估DON作为一种强效中枢神经系统（催吐、厌食）剂时，研究了其在对DON作用非常敏感的猪以及耐受性更强的绵羊体内的脑脊液（CSF）和血浆药代动力学。静脉给药后，在两种动物的脑脊液中都能很快检测到DON（不到2.5分钟），但绵羊的峰值水平（t-max）出现在5 - 10分钟，而猪则为30 - 60分钟。与绵羊（Vdβ = 0.19 l kg-1，毒素基本上局限于细胞外间隙）相比，猪体内DON非常快速且广泛的组织分布（Vdγ = 1.13 l kg-1）可能减缓了毒素扩散到脑脊液中的速度。曲线下面积计算表明，最终到达猪脑脊液中的毒素量约为绵羊脑脊液的2.5倍。尽管检测方法存在局限性，无法解析猪脑脊液中缓慢的终末相（γ），但静脉给药后血浆曲线中明显可见，两种动物的血脑脊液DON水平之间存在良好的关系。给猪口服DON后，观察到血浆和脑脊液DON水平之间密切相关。给药后长达20小时都能在脑脊液中检测到该毒素。
