Pensel Patricia E, Elissondo Natalia, Gambino Guillermo, Gamboa Gabriela Ullio, Benoit J P, Elissondo María C
Laboratorio de Zoonosis Parasitarias, Instituto de Investigaciones en Producción, Sanidad y Ambiente (IIPROSAM), Fac. Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
Laboratorio de Análisis Clínicos Santisteban, 7000 Tandil, Buenos Aires, Argentina.
Vet Parasitol. 2017 Oct 15;245:62-70. doi: 10.1016/j.vetpar.2017.08.011. Epub 2017 Aug 19.
Human cystic echinococcosis is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s. l.). Although benzimidazole compounds such as albendazole (ABZ) and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, new strategies are required to improve treatment of human cystic echinococcosis. The goals of the current study were as follows: (i) to evaluate the in vitro efficacy of the 5-fluorouracil (5-FU) and ABZ combination against E. granulosus s. l. protoscoleces and cysts, (ii) to compare the clinical efficacy of 5-FU alone or in combination with ABZ in infected mice. The combination of 5-FU+ABZ had a stronger in vitro effect against larval stage than that did both drugs alone. Even at the lowest concentration of 5-FU+ABZ combination (1μg/ml), the reduction of the viability of protoscoleces and cysts was greater than that observed with drugs alone at 10μg/ml. The results were confirmed at the ultrastructural level by scanning electron microscopy. These data helped to justify the in vivo investigations assessing the therapeutic potential of the combination of 5-FU and ABZ suspension in CF-1 mice infected with E. granulosus sensu stricto (s. s.) metacestodes. Treatment with 5-FU (10mg/kg) or 5-FU (10mg/kg) + ABZ suspension (5mg/kg) reduced the weight of cysts recovered from mice compared with control groups. Interestingly, the effect of 5-FU given weekly for 5 consecutive weeks was comparable to that observed with ABZ suspension under a daily schedule during 30days. Co-administration of 5-FU with ABZ did not enhance the in vivo efficacy of drugs alone calculated in relation to cysts weights. However, the combination provoked greater ultrastructural alterations compared to the monotherapy. In conclusion, we demonstrated the efficacy of 5-FU either alone or co-administrated with ABZ against murine experimental cystic echinococcosis. Since 5-FU treatments did not cause toxic effect in mice, further in vivo studies will be performed by adjusting the dosage and the frequency of treatments.
人体囊型包虫病是由细粒棘球绦虫广义种幼虫阶段引起的一种人畜共患病。尽管苯并咪唑类化合物如阿苯达唑（ABZ）和甲苯达唑一直是该病化疗的基石，但治疗后往往无法完全康复。因此，需要新的策略来改善人体囊型包虫病的治疗。本研究的目的如下：（i）评估5-氟尿嘧啶（5-FU）与ABZ联合用药对细粒棘球绦虫广义种原头节和囊肿的体外疗效，（ii）比较5-FU单独用药或与ABZ联合用药在感染小鼠中的临床疗效。5-FU+ABZ联合用药在体外对幼虫阶段的作用比两种药物单独使用时更强。即使在5-FU+ABZ联合用药的最低浓度（1μg/ml）下，原头节和囊肿活力的降低也大于单独使用药物在10μg/ml时的观察结果。扫描电子显微镜在超微结构水平上证实了这些结果。这些数据有助于证明在体内研究中评估5-FU与ABZ混悬液联合用药对感染狭义细粒棘球绦虫成虫的CF-1小鼠的治疗潜力。与对照组相比，用5-FU（10mg/kg）或5-FU（10mg/kg）+ABZ混悬液（5mg/kg）治疗可减轻从小鼠体内回收的囊肿重量。有趣的是，连续5周每周给予5-FU的效果与在30天内每日给予ABZ混悬液的效果相当。5-FU与ABZ联合给药相对于囊肿重量计算并未增强单独药物的体内疗效。然而，与单一疗法相比，联合用药引起了更大的超微结构改变。总之，我们证明了5-FU单独用药或与ABZ联合用药对小鼠实验性囊型包虫病有效。由于5-FU治疗未在小鼠中引起毒性作用，将通过调整治疗剂量和频率进行进一步的体内研究。
