Oxberry M E, Reynoldson J A, Thompson R C
Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
J Vet Pharmacol Ther. 2000 Jun;23(3):113-20. doi: 10.1046/j.1365-2885.2000.00254.x.
Trophozoites of the protozoan parasite Giardia duodenalis were exposed to various albendazole concentrations for 4 h, washed, fixed and incubated with antibodies raised against albendazole and its two major metabolites albendazole sulphoxide and albendazole sulphone. Tubulin antibodies were also used. A peroxidase- or FITC-conjugated secondary antibody was used to detect the primary antibody with transmission electron microscopy or confocal laser scanning microscopy, respectively. Albendazole, a benzimidazole compound, was detected in the mid-dorsal region of trophozoites, albendazole sulphoxide in the posterior-dorsal region and albendazole sulphone in clusters above the median bodies. Tubulin was recognised in the ventral disk. This is the first indication that G. duodenalis may be capable of metabolising albendazole and the potential path of the metabolised drug traced within the trophozoite. Fluorescence measurements revealed that albendazole sulphoxide binding decreased and albendazole sulphone binding increased with exposure of the trophozoites to increasing albendazole concentration. This indicates that if albendazole was being metabolised by trophozoites, it occurred to a greater extent following exposure to higher albendazole concentrations.
将原生动物寄生虫十二指肠贾第虫的滋养体暴露于不同浓度的阿苯达唑中4小时，洗涤、固定后，与针对阿苯达唑及其两种主要代谢产物阿苯达唑亚砜和阿苯达唑砜产生的抗体一起孵育。还使用了微管蛋白抗体。分别用与过氧化物酶或异硫氰酸荧光素（FITC）偶联的二抗，通过透射电子显微镜或共聚焦激光扫描显微镜检测一抗。在滋养体的中背部区域检测到阿苯达唑（一种苯并咪唑化合物），在后背区域检测到阿苯达唑亚砜，在中体上方的簇中检测到阿苯达唑砜。在腹盘处识别出微管蛋白。这是首次表明十二指肠贾第虫可能能够代谢阿苯达唑，并在滋养体内追踪到代谢药物的潜在途径。荧光测量结果显示，随着滋养体暴露于阿苯达唑浓度的增加，阿苯达唑亚砜的结合减少，而阿苯达唑砜的结合增加。这表明，如果阿苯达唑被滋养体代谢，那么在暴露于较高阿苯达唑浓度后，代谢程度会更高。
