Borges Adolfo, Silva Sylvia, Op den Camp Huub J M, Velasco Elena, Alvarez Marco, Alfonzo Marcelo J M, Jorquera Alicia, De Sousa Leonardo, Delgado Olinda
Institute of Experimental Medicine, Central University of Venezuela, Box 50587, Sabana Grande, Caracas 1051, Venezuela.
Parasitol Res. 2006 Jul;99(2):167-73. doi: 10.1007/s00436-006-0133-z. Epub 2006 Mar 15.
Leishmania parasites are sensitive to peptides with antimicrobial and ion-channel inhibitory activity. Because scorpion venoms are rich sources of such peptides, the leishmanicidal effect of Tityus discrepans venom was investigated. A negative correlation between cell growth and venom concentration was observed for venom-treated cultures of Leishmania (L.) mexicana mexicana promastigotes; 50% growth inhibition was obtained at 0.4 microg/ml. Light microscopy showed rounded, highly vacuolated L. (L.) m. mexicana cells with impaired flagellar motion after 15 min of incubation at 35 microg/ml. Ultrastructural studies confirmed an intense cytoplasm vacuolation and also enlargement of the flagellar pocket. Survival rates for New World Leishmania promastigotes (75% venom effective concentration, microg/ml) obtained after acute (1 h) venom toxicity tests were: L. (L.) m. mexicana (2.3), Leishmania (V.) braziliensis (11.3), and Leishmania (L.) chagasi (56.2). Heat (90 degrees C) treatment of venom and fraction TdII abolished most of their leishmanicidal effect. Acute toxicity assays performed with Sephadex G-50 fractions indicated that leishmanicidal activity is associated with the venom lowest molecular mass components (2.8-7.4 kDa), as determined by MALDI-TOF mass spectrometry.
利什曼原虫寄生虫对具有抗菌和离子通道抑制活性的肽敏感。由于蝎毒是这类肽的丰富来源,因此对差异泰氏蝎毒的杀利什曼原虫作用进行了研究。对于经毒液处理的墨西哥利什曼原虫前鞭毛体培养物,观察到细胞生长与毒液浓度之间呈负相关;在0.4微克/毫升时可获得50%的生长抑制率。光学显微镜显示,在35微克/毫升下孵育15分钟后,墨西哥利什曼原虫细胞呈圆形,高度空泡化,鞭毛运动受损。超微结构研究证实了强烈的细胞质空泡化以及鞭毛囊的扩大。在急性(1小时)毒液毒性试验后获得的新大陆利什曼原虫前鞭毛体的存活率(75%毒液有效浓度,微克/毫升)为:墨西哥利什曼原虫(2.3)、巴西利什曼原虫(11.3)和恰加斯利什曼原虫(56.2)。毒液和组分TdII经加热(90摄氏度)处理后,其大部分杀利什曼原虫作用消失。用葡聚糖G - 50组分进行的急性毒性试验表明,杀利什曼原虫活性与毒液的最低分子量组分(2.8 - 7.4千道尔顿)有关,这是通过基质辅助激光解吸电离飞行时间质谱法测定的。