Fonseca-Salamanca F, Martínez-Grueiro M M, Martínez-Fernández A R
Department of Parasitology, Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain.
Parasitol Res. 2003 Oct;91(4):321-4. doi: 10.1007/s00436-003-0974-7. Epub 2003 Sep 12.
The nematocidal activity of a broad-spectrum antiparasitic agent, nitazoxanide [( N-(5-nitrothiazol-2-gammal)salicylamide; NTZ], was evaluated in both in vitro and in vivo models using Caenorhabditis elegans, Heligmosomoides polygyrus and Trichinella spiralis. In vitro, NTZ (100 muM) exhibited a low activity against C. elegans and had no effect on embryonation and hatching of H. polygyrus eggs. At concentrations of 100 and 50 muM, the inhibition of excretion/secretion of acetylcholinesterase and acid phosphatase of adult H. polygyrus by NTZ was variable. The in vitro effects of mebendazole (5 muM), albendazole (1 muM) and levamisole (10 muM) were superior to those of NTZ. In mice, NTZ at 1 g/kg proved to be inactive against preadults of T. spiralis whereas mebendazole at 10 mg/kg reduced the worm burden by up to 83%. NTZ at 1 g/kg per day for 3 consecutive days showed a low activity against adults of H. polygyrus (21% reduction). Levamisole, at a single dose of 10 mg/kg, reduced the worm burden by up to 89.9%. The results of this study suggest that NTZ would not have met criteria of a candidate compound.
使用秀丽隐杆线虫、多房棘球绦虫和旋毛虫,在体外和体内模型中评估了一种广谱抗寄生虫药硝唑尼特[N-(5-硝基噻唑-2-基)水杨酰胺;NTZ]的杀线虫活性。在体外,NTZ(100 μM)对秀丽隐杆线虫表现出低活性,对多房棘球绦虫虫卵的胚胎发育和孵化没有影响。在100和50 μM浓度下,NTZ对成年多房棘球绦虫乙酰胆碱酯酶和酸性磷酸酶排泄/分泌的抑制作用是可变的。甲苯咪唑(5 μM)、阿苯达唑(1 μM)和左旋咪唑(10 μM)的体外效果优于NTZ。在小鼠中,1 g/kg的NTZ对旋毛虫的成虫前期没有活性,而10 mg/kg的甲苯咪唑可使虫负荷减少高达83%。连续3天每天1 g/kg的NTZ对多房棘球绦虫成虫表现出低活性(减少21%)。单次剂量10 mg/kg的左旋咪唑可使虫负荷减少高达89.9%。本研究结果表明,NTZ不符合候选化合物的标准。