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首页> 外文期刊>International immunopharmacology >Sesquiterpene lactone potentiates the immunomodulatory, antiparasitic and cardioprotective effects on anti-Trypanosoma cruzi specific chemotherapy
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Sesquiterpene lactone potentiates the immunomodulatory, antiparasitic and cardioprotective effects on anti-Trypanosoma cruzi specific chemotherapy

机译：SesquiterPene内酯强调免疫调节，抗孕腺和心脏保护作用对抗蛋白酶瘤Cruzi特异性化疗

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摘要

We investigated the immunomodulatory, antiparasitic and cardioprotective effects of a sesquiterpene lactone (SL) administered alone or combined with benznidazole (Bz), in a murine model of Chagas' disease by in vitro and in vivo assays. Antiparasitic and cytotoxic potential of tagitinin C (SL) and Bz were tested in vitro against T. cruzi epimastigotes and cardiomyocytes. Swiss mice challenged with T. cruzi were also treated for 20 days with tagitinin C (10 mg/kg) alone and combined with Bz (100 mg/kg). Tagitinin C exhibited a higher antiparasitic (IC50: 1.15 mu M) and cytotoxic (CC50 at 6.54 mu M) potential than Bz (IC50: 35.81 mu M and CC50, 713.5 mu M, respectively). When combined, these drugs presented an addictive interaction, determining complete suppression of parasitemia and parasitological cure in all infected mice (100%) compared to those receiving Bz alone (70%). Anti-T. cruzi immunoglobulin G, and pro-inflammatory cytokines IFN-gamma and TNF-alpha levels were reduced in animals treated with tagitinin C combined with Bz, while IL-10 production was unaffected. Heart inflammation was undetectable in 90% of the animals receiving this combination, while only 50% of the animals receiving Bz alone showed no evidence of myocarditis. Together, our findings indicated that the combination of tagitinin C and Bz exerts potent antiparasitic, immunomodulatory and cardioprotective effects. Due to the remarkable suppression of parasitemia and high parasitological cure, this combination was superior to Bz monotherapy, indicating a high potential for the treatment of Chagas's disease.
机译：通过体外和体内测定，通过体外和体内测定，研究单独给药或与苯并咪唑（BZ）联合苯并咪唑（BZ）的免疫调节，抗寄生虫和心脏保护作用。在体外测试标记蛋白蛋白C（SL）和BZ的抗遗传性和细胞毒性潜力对抗T.Cruzi ePimastigotes和心肌细胞。用T.Cruzi挑战的瑞士小鼠也用标记蛋白C（10mg / kg）处理20天并与BZ（100mg / kg）合并。 Tagitinin C表现出比BZ的更高的抗抗原性（IC50：1.15μm）和细胞毒性（CC50，CC50，分别为35.81μm和CC50，713.5μm。结合时，这些药物呈现成瘾的相互作用，与单独接受BZ（70％）相比，确定所有感染的小鼠（100％）中的寄生虫和寄生虫治疗的完全抑制。抗T。在用标记蛋白C合并与BZ处理的动物处理的动物中减少了Cruzi免疫球蛋白G和促炎细胞因子IFN-Gamma和TNF-α水平，而IL-10产生不受影响。在接受这种组合的90％的动物中，心脏炎症不可检测到，而仅接受BZ的动物只有50％的动物没有表现出心肌炎的证据。我们的研究结果在一起表明Tagitinin C和BZ的组合施加有效的抗遗传性，免疫调节和心脏保护作用。由于血糖血症和高寄生虫治疗的显着抑制，这种组合优于BZ单疗法，表明抑制棘伽士疾病的潜力很高。

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