Poli Giorgio, Martino Piera Anna, Villa Stefania, Carcassola Gabriella, Giannino Maria Laura, Dall'Ara Paola, Pollera Claudia, Iussich Selina, Tranquillo Vito M, Bareggi Silvio, Mantegazza Paolo, Ponti Wilma
Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Facoltà di Medicina Veterinaria, Università di Milano, Milan, Italy.
Arzneimittelforschung. 2004;54(7):406-15. doi: 10.1055/s-0031-1296992.
Among transmissible spongiform encephalopathies (TSE), particularly dreadful are the bovine spongiform encephalopathy (BSE), because of its epidemic character, and the new variant of Creutzfeldt-lakob disease (vCJD) in man, possibly related to BSE prion, through the intake of infected food. To treat TSE, many potentially therapeutic agents have been tested: some of them, among which is Congo Red (CAS 573-58-0, CR), delayed the onset of symptoms in scrapie-infected rodents, and some CR derivatives proved to be effective in vitro. The capacity of a synthesized CR derivative (CR-A) and of the aromatic central benzidine rings of CR (CR-B) to abrogate scrapie-induced disease in experimentally infected hamsters was assayed. CR, used as reference substance, administered i.c. after pre-incubation with the scrapie inoculum, was strongly effective in slowing the progression of the infection, while both CR-A and CR-B, administered alone or together, were not effective. Both CR-A and CR, when administered by subcutaneous route in i.c. scrapie-infected animals. prolonged the survival time in comparison to controls; CR-B was not effective. Moreover, both CR and CR-A were very effective in prolonging the survival time of i.p. scrapie-infected hamsters. The hypothesis of possible different mechanisms of interaction between CR or CR-A and the scrapie agent related to the chemical structures of the molecules is discussed.
在传染性海绵状脑病(TSE)中,牛海绵状脑病(BSE)因其流行性,以及人类新型克雅氏病(vCJD)可能通过摄入受感染食物与BSE朊病毒有关,故而尤为可怕。为治疗TSE,人们测试了许多潜在治疗药物:其中一些药物,如刚果红(CAS 573-58-0,CR),可延缓瘙痒病感染啮齿动物症状的出现,一些CR衍生物在体外已被证明有效。对一种合成的CR衍生物(CR-A)以及CR的芳香中心联苯环(CR-B)在实验感染仓鼠中消除瘙痒病诱导疾病的能力进行了测定。用作参考物质的CR在与瘙痒病接种物预孵育后经脑内给药,对减缓感染进程非常有效,而单独或联合给药的CR-A和CR-B均无效。CR-A和CR经皮下途径给药于脑内感染瘙痒病的动物时,与对照组相比延长了存活时间;CR-B无效。此外,CR和CR-A在延长腹腔感染瘙痒病仓鼠的存活时间方面都非常有效。文中讨论了CR或CR-A与瘙痒病病原体之间可能存在与分子化学结构相关的不同相互作用机制的假设。