Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo

他克莫司是一种雷帕霉素靶蛋白抑制剂,在体内和体外均具有抗囊型包虫病作用

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作者:Muzhabaier Muhedier, Jintian Li, Hui Liu, Guizhi Ma, Kuerbannisha Amahong, Renyong Lin, Guodong Lü

Abstract

In view of a growing need for new treatment options for human cystic echinococcosis (CE), we aimed to investigate the efficacy of mTOR pathway inhibitors against CE in vitro and in vivo. Among the seven mTOR inhibitors evaluated, tacrolimus (TAC) showed significant dose- and time-dependent killing of cultured protoscoleces and cysts in vitro. Notably, the oral administration of TAC (4 mg/kg/day) to CE mice model highly effectively reduced both the weight and number of parasitic cysts. Transmission electron microscopy revealed that TAC destroys the ultrastructure of cysts, both in vitro and in vivo. Furthermore, TAC had no significant effect on blood glucose, body weight, liver, or kidney functions in mice. We further observed that the ATP levels and glucose content of cysts reduced upon TAC treatment, indicating that inhibiting mTORC1 activity possibly affects glucose metabolism in the cysts of mice. Based on our experimental data, TAC emerged as a promising anti-cyst drug that efficiently inhibits the growth of cysts.

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