Wieland E, Neumann H G
Arch Toxicol. 1978 Feb 21;40(1):17-35. doi: 10.1007/BF00353276.
trans-4-Aminostilbene derivatives exhibit higher acute and chronic toxicity than 4-aminobibenzyl derivatives. Yet, trans-4-aminostilbene produced less methemoglobin in female Wistar rats than 4-aminobibenzyl. This cannot be explained by differences in N-oxidation since trans-4-nitrosostilbene was also less efficient than 4-nitrosobibenzyl. The fate of intravenously injected, highly and specifically 3H-labeled trans-4-aminostilbene, cis-4-aminostilbene, 4-aminobibenzyl, trans-4-nitrosostilbene and 4-nitrosobibenzyl was investigated. The results indicate that trans-4-aminostilbene and 4-aminobibenzyl are N-oxidized to a similar extent and primary activation products of trans-4-aminostilbene appear even faster in the blood. However, intermediates originating during methemoglobin formation are more reactive and covalently bind to hemoglobin 2--3 times as much with trans-stilbene as compared to bibenzyl derivatives. As a consequence the availability of these intermediates in the cyclic process and thus methemoglobin formation is reduced. Therefore, binding to hemoglobin rather than levels of methemoglobin appears to be an indicator for the availability and reactivity of some activated aromatic amine metabolites.
反式-4-氨基芪衍生物比4-氨基联苄衍生物表现出更高的急性和慢性毒性。然而，在雌性Wistar大鼠中，反式-4-氨基芪产生的高铁血红蛋白比4-氨基联苄少。由于反式-4-亚硝基芪也比4-亚硝基联苄效率低，这无法用N-氧化的差异来解释。研究了静脉注射的、高度特异性的3H标记的反式-4-氨基芪、顺式-4-氨基芪、4-氨基联苄、反式-4-亚硝基芪和4-亚硝基联苄的代谢情况。结果表明，反式-4-氨基芪和4-氨基联苄的N-氧化程度相似，反式-4-氨基芪的主要活化产物在血液中出现得更快。然而，高铁血红蛋白形成过程中产生的中间体更具反应性，与联苄衍生物相比，反式芪与血红蛋白的共价结合量是其2至3倍。因此，这些中间体在循环过程中的可用性以及高铁血红蛋白的形成减少。因此，与血红蛋白的结合而非高铁血红蛋白的水平似乎是某些活化芳香胺代谢产物可用性和反应性的指标。
