Nicolao María Celeste, Elissondo María Celina, Denegri Guillermo M, Goya Alejandra B, Cumino Andrea C
Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Departamento de Toxinas Marinas, Laboratorio Regional Mar del Plata, Centro Regional Buenos Aires Sur, Servicio Nacional de Sanidad y Calidad Agroalimentaria (SENASA), Mar del Plata, Argentina.
Antimicrob Agents Chemother. 2014 Sep;58(9):5146-54. doi: 10.1128/AAC.02113-13. Epub 2014 Jun 16.
Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.
囊型包虫病是由细粒棘球绦虫幼虫阶段引起的一种人畜共患感染。目前化疗采用苯并咪唑类药物；然而，40%的病例治疗效果不佳。针对这些难题，需要新的治疗手段来优化人类患者的治疗。本研究旨在探讨他莫昔芬（TAM）对细粒棘球绦虫的体外和体内作用。此外，还讨论了TAM敏感性的可能机制，涉及钙稳态、P-糖蛋白抑制以及对假定类固醇受体的拮抗作用。治疗24小时后，低微摩尔浓度范围（10至50μM）的TAM可抑制细粒棘球绦虫原头蚴和囊尾蚴的存活。此外，我们还证实了该药物的化疗和化学预防药理作用。以20mg/kg体重的剂量率给药时，TAM可诱导小鼠对感染产生保护作用。在临床疗效研究中，与对照组小鼠收集的囊肿相比，给囊肿形成3或6个月的小鼠施用20mg/kg TAM后，观察到囊肿重量减轻。由于高剂量TAM的副作用在临床试验中已有大量记录，使用低剂量该药物作为短期治疗可能是治疗人类囊型包虫病的一种新的替代方法。
