Artesunate and artemether are effective fasciolicides in the rat model and in vitro
Artesunate and artemether are effective fasciolicides in the rat model and in vitro
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DOI：
10.1093/jac/dkl125
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发表时间：
2006-06-01
影响因子：
5.2
通讯作者：
Utzinger, Jurg
中科院分区：
文献类型：
--
作者：
Keiser, Jennifer;Shu-Hua, Xiao;Utzinger, Jurg
目的：研究青蒿琥酯和蒿甲醚对大鼠肝片吸虫模型和体外抗肝片吸虫作用。方法：用青蒿琥酯、蒿甲醚和双氢青蒿素3种不同剂量的青蒿琥酯、蒿甲醚和双氢青蒿素在体外染毒72 h，雌性Wistar大鼠从感染后3周或10~14周开始单剂量口服青蒿琥酯和蒿甲醚(100~400 mg/kg)，比较感染后和未治疗对照组大鼠的虫体减重情况。结果：青蒿琥酯、蒿甲醚和双氢青蒿素在体外作用72 h至10 mU g/m L，表现为虫体活动能力差、虫体肿胀、表面粗糙、被膜损伤和起泡。用青蒿琥酯400 mg/kg和蒿甲醚200 mg/kg对感染成虫的肝片吸虫大鼠的减虫率为100%。青蒿琥酯200 mg/kg和蒿甲醚200 mg/kg给携带肝片吸虫幼虫的大鼠，虫体负担分别减少46%和82%。大鼠注射200 mg/kg青蒿琥酯24小时后，肝片吸虫从胆管中恢复正常活动，扫描电子显微镜观察未见明显损伤。治疗72h后，肝片吸虫的活动度很低，被膜和脊椎局部肿胀。结论：青蒿琥酯和蒿甲醚具有良好的杀肝片活性，后者对宿主有较好的耐受性。
Objectives: To study the fasciocidal properties of artesunate and artemether in the rat model and in vitro.Methods: Adult Fasciola hepatica were exposed in vitro to 1, 10 and 100 mu g/mL of artesunate, artemether and dihydroartemisinin for 72 h. Female Wistar rats were administered a single oral dose of artesunate and artemether (100-400 mg/kg) commencing 3 or 10-14 weeks post-infection and worm burden reductions were assessed against infected but untreated control rats. F. hepatica were also observed by scanning electron microscopy (SEM) after recovery from bile ducts of rats given a single oral dose of 200 mg/kg artesunate 24 and 72 h post-treatment.Results: F. hepatica exposed for 72 h to 10 mu g/mL of artesunate, artemether and dihydroartemisinin in vitro showed poor mobility, swelling of the worm body, roughness, damage of the tegument and blebbing. Exposure to drug concentrations of 100 mu g/mL resulted in the death of all F. hepatica by 72 h. One hundred percent worm burden reductions were achieved in rats infected with adult F. hepatica after treatment with artesunate and artemether at 400 and 200 mg/kg, respectively. Administration of artesunate and artemether at a dose of 200 mg/kg to rats harbouring juvenile F. hepatica resulted in worm burden reductions of 46% and 82%, respectively. F. hepatica recovered from rats' bile ducts 24 h after administration of 200 mg/kg artesunate showed normal activity and SEM observations revealed that there was no visible damage. Seventy-two hours post-treatment F. hepatica displayed very poor mobility and there was focal swelling of the tegument and spines.Conclusions: Artesunate and artemether exhibit promising fasciocidal activities, with the latter showing better tolerability by the hosts.