Woolsey Ian David, Fredensborg Brian L, Jensen Per M, Kapel Christian M O, Meyling Nicolai V
Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871, Frederiksberg C, Denmark,
Parasitol Res. 2015 Jul;114(7):2777-80. doi: 10.1007/s00436-015-4477-0. Epub 2015 Apr 18.
Invertebrate models provide several important advantages over their vertebrate counterparts including fewer legislative stipulations and faster, more cost-effective experimental procedures. Furthermore, various similarities between insect and mammalian systems have been highlighted. To obtain maximum use of invertebrate models in pharmacology, their fidelity as analogues of vertebrate systems requires verification. We utilised a flour beetle (Tenebrio molitor)-tapeworm (Hymenolepis diminuta) model to evaluate the efficacy of known anthelmintic compounds, praziquantel, mebendazole and levamisole against H. diminuta cysticercoid larvae in vitro. Inhibition of cysticercoid activity during the excystation procedure was used as a proxy for worm removal. The effects of the three compounds mirrored their relative efficacy in treatment against adult worms in mammalian systems; however, further study is required to determine the fidelity of this model in relation to dose administered. The model precludes comparison of consecutive daily administration of pharmaceuticals in mammals due to cysticercoids not surviving outside of the host for multiple days. Treatment of beetles in vivo, followed by excystation of cysticercoids postdissection could potentially allow for such comparisons. Further model validation will include analysis of pharmaceutical efficacy in varying H. diminuta isolates and pharmaceutical dilution in solvents other than water. Notwithstanding, our results demonstrate that this model holds promise as a method to efficiently identify promising new cestocidal candidates.
与脊椎动物模型相比，无脊椎动物模型具有几个重要优势，包括较少的立法规定以及更快、更具成本效益的实验程序。此外，昆虫和哺乳动物系统之间的各种相似性也已得到强调。为了在药理学中最大程度地利用无脊椎动物模型，需要验证它们作为脊椎动物系统类似物的保真度。我们利用黄粉虫（黄粉虫）-绦虫（微小膜壳绦虫）模型在体外评估已知驱虫化合物吡喹酮、甲苯咪唑和左旋咪唑对微小膜壳绦虫囊尾蚴幼虫的疗效。在脱囊过程中对囊尾蚴活性的抑制被用作驱虫的替代指标。这三种化合物的效果反映了它们在哺乳动物系统中治疗成虫的相对疗效；然而，需要进一步研究以确定该模型在给药剂量方面的保真度。由于囊尾蚴在宿主体外无法存活多天，该模型无法比较哺乳动物中连续每日给药的情况。对甲虫进行体内治疗，然后在解剖后对囊尾蚴进行脱囊，可能会允许进行此类比较。进一步的模型验证将包括分析不同微小膜壳绦虫分离株中的药物疗效以及在水以外的溶剂中的药物稀释情况。尽管如此，我们的结果表明，该模型有望成为一种有效识别有前景的新型杀绦虫候选物的方法。
