Loiseau P M, Jennings F W, Lubert P, Wolf J G
Biologie et Contrôle des Organismes Parasites, Faculté de Pharmacie, Université de Paris-Sud, Châtenay-Malabry, France.
Parasitol Res. 1996;82(5):477-80. doi: 10.1007/s004360050148.
Topical application and intraperitoneal administration of spiroarsoranes were carried out to cure central nervous system (CNS) trypanosomiasis in the chronic Trypanosoma brucei GVR 35 mouse model. Topical application appeared more efficient than intraperitoneal injection. The periods of aparasitaemia after treatment were longer but none of the mice was permanently cured. Combination treatment with eflornithine (DFMO) and the spiroarsoranes failed to show any synergistic effect. In addition, spiroarsorane I was evaluated against the T. b. rhodesiense KETRI 2634 strain, whereby 60-mg/kg treatment produced a noticeable prolongation of the life span of trypanosome-positive animals. These in vivo results suggests that the spiroarsoranes have difficulty in crossing the blood-brain barrier (BBB) and clearing the parasites from the CNS or, alternatively, that these strains are less sensitive to pentavalent arsenicals than the T. b. brucei CMP fast strain, which in the present study was more sensitive to spiroarsoranes whose lipophilicity corresponded to a log-P value ranging from 2.5 to 3.7.
在布氏锥虫GVR 35慢性小鼠模型中，通过局部应用和腹腔注射螺旋砷烷来治疗中枢神经系统（CNS）锥虫病。局部应用似乎比腹腔注射更有效。治疗后无寄生虫血症的持续时间更长，但没有一只小鼠被永久治愈。依氟鸟氨酸（DFMO）与螺旋砷烷联合治疗未显示出任何协同作用。此外，对螺旋砷烷I进行了针对布氏罗得西亚锥虫KETRI 2634菌株的评估，结果显示60 mg/kg的治疗剂量使锥虫阳性动物的寿命显著延长。这些体内实验结果表明，螺旋砷烷难以穿过血脑屏障（BBB）并清除中枢神经系统中的寄生虫，或者说，这些菌株对五价砷化合物的敏感性低于布氏布氏锥虫CMP快速菌株，在本研究中，布氏布氏锥虫CMP快速菌株对脂溶性对应log-P值为2.5至3.7的螺旋砷烷更敏感。
