In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
复制标题
DOI：
10.1128/aac.02113-13
复制
发表时间：
2014-09-01
影响因子：
4.9
通讯作者：
Cumino, Andrea C.
中科院分区：
文献类型：
--
作者：
Celeste Nicolao, Maria;Celina Elissondo, Maria;Cumino, Andrea C.
囊状棘球蚴病是由细粒棘球绦虫的幼虫阶段引起的人畜共患传染病。化疗目前使用苯并咪唑类药物;然而，40%的病例反应不佳。关于这些困难，需要新的治疗工具来优化人类的治疗。本工作的目的是探讨三苯氧胺（TAM）在体外和体内抗大肠杆菌的作用。颗粒状。此外，TAM的易感性的可能机制进行了讨论，在钙稳态，P-糖蛋白抑制，和拮抗剂对一个假定的类固醇受体的影响。在处理24小时后，TAM在低微摩尔浓度范围（10至50 μ M），抑制E.颗粒体原绦虫和后绦虫。此外，我们证明了药物的化疗和化学预防药理作用。在20 mg/kg体重的剂量率下，TAM在小鼠中诱导针对感染的保护。在临床有效性研究中，与从对照小鼠中采集的囊肿相比，在3或6个月期间形成囊肿的小鼠中，在给予20 mg/kg后观察到囊肿重量减轻。由于高TAM剂量的副作用已在临床试验中大量记录，因此使用低剂量的这种药物作为短期治疗可能是治疗人类囊性包虫病的一种新的替代方法。
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 mu M), 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.