Botros Sanaa S, Mahmoud Madiha R, Moussa Mona M, Nosseir Mona M
Pharmacology Department, Theodor Bilharz Research Institute, P.O. Box 30, Imbaba, 12411 Giza, Egypt.
J Infect. 2007 Nov;55(5):470-7. doi: 10.1016/j.jinf.2007.07.022. Epub 2007 Sep 14.
To investigate immune mechanisms possibly involved in the amelioration of histopathological changes in livers of Schistosoma mansoni-infected mice treated with artemether (ART), including liver functions and apoptotic changes.
Male CD-1 Swiss albino mice were infected with Schistosoma mansoni and treated with praziquantel (PZQ) 6 weeks post-infection (PI) (500 mg/kg/day x2) and/or ART in double dose (each of 400 mg/kg) 4 and 6 weeks PI. Parasitological parameters, liver functions and histopathological changes including T-lymphocyte profile and apoptotic changes were assessed.
Eight weeks PI, although the reduction in worm burden in mice treated with ART plus PZQ was comparable to that in PZQ-treated mice, yet there was complete absence of eggs and typical granulomas. The ratio of T-helper/cytotoxic cells was in favor of T-helper in infected control and in mice treated with both drugs. This ratio was 0.9:1 and 0.7:1 in PZQ and ART-treated groups, respectively, with moderate apoptotic changes in the latter. All biochemical parameters expressing liver function were improved with all treatment regimens.
Administration of ART in addition to PZQ resulted in absence of eggs and typical granulomas with less apoptotic changes than in ART-treated mice. Improved liver functions with higher apoptosis in ART-treated mice may suggest enhanced necrotic cell death/regenerative changes.
研究青蒿琥酯(ART)治疗曼氏血吸虫感染小鼠后,肝脏组织病理学变化改善可能涉及的免疫机制,包括肝功能和凋亡变化。
雄性CD-1瑞士白化小鼠感染曼氏血吸虫,感染后6周(PI)用吡喹酮(PZQ)治疗(500mg/kg/天×2)和/或在感染后4周和6周用双倍剂量(各400mg/kg)的ART治疗。评估寄生虫学参数、肝功能和组织病理学变化,包括T淋巴细胞谱和凋亡变化。
感染后8周,虽然ART加PZQ治疗的小鼠虫体负荷降低与PZQ治疗的小鼠相当,但完全没有虫卵和典型肉芽肿。在感染对照组和两种药物治疗的小鼠中,辅助性T细胞/细胞毒性细胞的比例有利于辅助性T细胞。在PZQ和ART治疗组中,该比例分别为0.9:1和0.7:1,后者有中度凋亡变化。所有表达肝功能的生化参数在所有治疗方案下均得到改善。
除PZQ外给予ART可导致无虫卵和典型肉芽肿,且凋亡变化比ART治疗的小鼠少。ART治疗的小鼠肝功能改善且凋亡增加,这可能提示坏死性细胞死亡/再生变化增强。