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三氯生和载三氯生脂质体纳米粒治疗急性实验性弓形虫病。

Triclosan and triclosan-loaded liposomal nanoparticles in the treatment of acute experimental toxoplasmosis.

机构信息

Medical Parasitology Department, Faculty of Medicine, Alexandria University, Egypt.

Medical Parasitology Department, Faculty of Medicine, Alexandria University, Egypt.

出版信息

Exp Parasitol. 2015 Feb;149:54-64. doi: 10.1016/j.exppara.2014.12.007. Epub 2014 Dec 9.

Abstract

Efficacy of triclosan (TS) and TS-loaded liposomes against the virulent strain of Toxoplasma gondii (T. gondii) was evaluated. Swiss albino mice were intraperitoneally infected with 10(4) tachyzoites of RH HXGPRT(-) strain of T. gondii, then were orally treated with 150 mg/kg TS or 100 mg/kg TS liposomes twice daily for 4 days. Mice mortality, peritoneal and liver parasite burdens, viability, infectivity and ultrastructural changes of peritoneal tachyzoites of infected treated mice were studied, in comparison with those of infected non-treated controls. Drug safety was biochemically assessed by measuring liver enzymes and thyroxin. Both TS and TS liposomes induced significant reduction in mice mortality, parasite burden, viability and infectivity of tachyzoites harvested from infected treated mice. Scanning electron microscopy of treated tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion. Transmission electron microscopy showed that treated tachyzoites were intracellularly distorted, had cytoplasmic vacuolation, discontinuous plasma membranes, nuclear abnormalities and disrupted internal structures. Besides, in TS liposomes-treated subgroup, most tachyzoites were seen intracellularly with complete disintegration of the parasite plasma and nuclear membranes, with complete destruction of the internal structures. Biochemical safety of TS and TS liposomes was proven. Accordingly, TS can be considered as a promising alternative to the standard therapy for treating acute murine toxoplasmosis. Liposomal formulation of TS enhanced its efficacy and allowed its use in a lower dose.

摘要

评估了三氯生(TS)和负载三氯生的脂质体对强毒株弓形虫(Toxoplasma gondii)的疗效。用 RH HXGPRT(-)株弓形虫 10(4)速殖子经腹腔感染瑞士白化小鼠,然后用 150mg/kg TS 或 100mg/kg TS 脂质体每日两次口服治疗 4 天。研究了感染治疗小鼠的腹膜和肝寄生虫负荷、存活率、感染性和腹膜速殖子的超微结构变化,并与感染未治疗对照组进行了比较。通过测量肝酶和甲状腺素来评估药物安全性。TS 和 TS 脂质体均显著降低了感染治疗小鼠的死亡率、寄生虫负荷、速殖子活力和感染性。用治疗后的速殖子进行扫描电子显微镜检查显示,变形、缩小、不规则、表面突起、侵蚀和剥落,除了顶端区域变形。透射电子显微镜显示,治疗后的速殖子在细胞内变形,细胞质空泡化,质膜不连续,核异常,内部结构破坏。此外,在 TS 脂质体治疗亚组中,大多数速殖子在细胞内观察到,寄生虫质膜和核膜完全崩解,内部结构完全破坏。证明了 TS 和 TS 脂质体的生化安全性。因此,TS 可被视为治疗急性鼠弓形体病的标准治疗的有前途的替代药物。TS 的脂质体制剂增强了其疗效,并允许使用较低剂量。

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