Alcalá-Canto Yazmin, Ibarra-Velarde Froylan, Sumano-Lopez Hector, Gracia-Mora Jesus, Alberti-Navarro Aldo
Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico, D.F. 04510, Mexico.
Parasitol Res. 2006 Apr;98(5):438-42. doi: 10.1007/s00436-005-0046-2. Epub 2006 Jan 6.
Using the film in situ zymography (FIZ) technique, it has been demonstrated that N-[N-(L: -3-trans-carboxyoxirane-2-carbonyl)-L: -leucyl]-agmatine (E-64) inhibits Fasciola hepatica proteolytic activity in vivo. The aim of this study was to establish the dose-response relationship of the inhibition of proteolysis as assessed by FIZ with E-64 at different dosages in a murine model of fasciolosis. Maximum effective inhibition of proteolysis was achieved at 50 mg/kg/day (87%). Mice treated with this dose survived for a mean of 10.92 days more than untreated controls, and their ova counts and egg viability were significantly (P<0.05) lower than this latter group. These results indicate that intraperitoneal administration of E-64 not only inhibited liver proteolytic activity in a dose-dependent manner but also produced anti-fecundity and anti-embryonation effects, delaying the progression of fasciolosis. Yet, residual proteolysis may suggest that other E-64-non-sensitive enzymes are involved, or that E-64-enzyme chemical interactions are only capable of a partial agonistic-like effect.
运用原位凝胶酶谱法（FIZ）技术已证实，N-[N-(L-3-反式-羧基环氧乙烷-2-羰基)-L-亮氨酰]-胍丁胺（E-64）在体内可抑制肝片吸虫的蛋白水解活性。本研究的目的是在小鼠肝片吸虫病模型中，确定通过FIZ评估的不同剂量E-64对蛋白水解抑制作用的剂量反应关系。在50 mg/kg/天的剂量下实现了对蛋白水解的最大有效抑制（87%）。接受该剂量治疗的小鼠比未治疗的对照组平均多存活10.92天，且其虫卵计数和卵活力显著低于后一组（P<0.05）。这些结果表明，腹腔注射E-64不仅以剂量依赖的方式抑制肝脏蛋白水解活性，还产生抗繁殖力和抗胚胎发育作用，延缓了肝片吸虫病的进展。然而，残余的蛋白水解可能表明还涉及其他对E-64不敏感的酶，或者E-64与酶的化学相互作用仅能产生部分类似激动剂的效应。
