Bergmann F, Soffer D, Yagen B
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem.
Toxicon. 1988;26(10):923-30. doi: 10.1016/0041-0101(88)90257-7.
T-2 toxin and its metabolites (resulting from enzymatic hydrolysis by rat brain homogenate) were applied to the midbrain of albino rats, either in solid form or dissolved in dimethyl sulfoxide (DMSO). Solid implants of HT-2 toxin and of T-2 triol were lethal in the range of 10-20 micrograms per rat, i.e. similar to the effect of T-2 toxin itself. For four further trichothecenes, the following decreasing order of toxicities was found: T-2 tetraol = iso-T-2 toxin greater than T-2 tetraol tetraacetate greater than T-2 toxin acetate. Implants of the last compound were the least toxic in the present series of trichothecenes; its LD50 value was nearly ten times higher than that of T-2 toxin. A similar gradation of toxicity was observed upon intracerebral injection of the compounds dissolved in DMSO. Here the only exception was the markedly reduced toxicity of T-2 toxin itself. From these data, the role of free 3 alpha- and 4 beta-hydroxyl groups has been evaluated. For subcutaneous applications, the largest ratio of LD50 values was 5, i.e. for the pair T-2 triol-T-2 tetraol tetraacetate. Among the signs of central intoxication, convulsions, adipsia and aphagia were marked. Pathological changes in the brain tissue, mainly involving necrotic, hemorrhagic and inflammatory lesions at the sites of application, were similar for all trichothecenes tested in this study.
将T-2毒素及其代谢产物（由大鼠脑匀浆酶解产生）以固体形式或溶解于二甲基亚砜（DMSO）中应用于白化大鼠的中脑。HT-2毒素和T-2三醇的固体植入物对每只大鼠的致死剂量在10 - 20微克范围内，即与T-2毒素本身的作用相似。对于另外四种单端孢霉烯族毒素，发现其毒性呈以下递减顺序：T-2四醇 = 异T-2毒素＞T-2四醇四乙酸酯＞T-2毒素乙酸酯。在本系列单端孢霉烯族毒素中，最后一种化合物的植入物毒性最小；其半数致死剂量（LD50）值几乎比T-2毒素高十倍。当脑内注射溶解于DMSO的化合物时，也观察到了类似的毒性分级。唯一的例外是T-2毒素本身的毒性明显降低。根据这些数据，对游离的3α-和4β-羟基的作用进行了评估。对于皮下给药，LD50值的最大比值为5，即T-2三醇 - T-2四醇四乙酸酯这一对。在中枢中毒的体征中，惊厥、拒饮和拒食较为明显。本研究中测试的所有单端孢霉烯族毒素在脑组织中的病理变化主要包括应用部位的坏死、出血和炎症性病变，这些变化相似。
