卡旦醇类磷脂类似物对阴道毛滴虫的影响

IF 1.4 4区 医学 Q3 PARASITOLOGY Experimental parasitology Pub Date : 2024-09-10 DOI:10.1016/j.exppara.2024.108839
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引用次数: 0

摘要

阴道毛滴虫是泌尿生殖道的一种原生寄生虫,是人类滴虫病的罪魁祸首,全世界约有 1.56 亿人受到这种性传播感染。这种病症在女性中更为明显,可导致流产、早产和不孕。这种疾病还可能导致更容易感染艾滋病毒、宫颈癌和前列腺癌。甲硝唑(MTZ)是一种治疗人类滴虫病的药物。有关孕期使用 MTZ 的人体研究数据有限。除了治疗的毒性外,一些分离株还对 MTZ 产生了抗药性。因此,有必要寻找对治疗滴虫病有活性的新化合物。在本研究中,我们报告了使用新型磷脂类似物所取得的结果。两种被命名为 LDT117 和 LDT134 的贲门醇类化合物对阴道毛滴虫具有活性,IC50 分别为 4.58 和 10.24 μM。这些化合物对培养的上皮细胞没有毒性。扫描电子显微镜观察发现,细胞变圆,鞭毛缩短,药物处理过的细胞表面出现突起。对处理过的细胞进行透射电子显微镜观察后发现,细胞质膜发生了改变,形成了出血点、突起、凹陷和空泡,细胞质中出现了髓鞘和空泡化。此外,经 LDT117 和 LDT134 复合物处理后,寄生虫的 TUNEL 呈阳性反应,表明寄生虫是通过类似细胞凋亡的机制死亡的。鉴于上述结果,有必要使用动物实验模型进行进一步的体内研究,以验证这些化合物对治疗人类滴虫病的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Effects of cardanol-based phospholipid analogs on Trichomonas vaginalis

Trichomonas vaginalis is a protist parasite of the urogenital tract, responsible for human trichomoniasis, an infection sexually transmitted that affects approximately 156 million people worldwide. This pathology is more evident in females and can cause miscarriages, premature births, and infertility. The disease can also lead to a greater predisposition to HIV infection and cervical and prostate cancer. Metronidazole (MTZ) is a drug that treats human trichomoniasis. The data from studies involving human subjects are limited regarding MTZ use during pregnancy. In addition to the toxicity of the treatment, some isolates have become resistant to MTZ. Therefore, searching for new compounds active for treating trichomoniasis becomes necessary. In the present study, we report results obtained using new phospholipid analogs. Two cardanol-based compounds designated LDT117 and LDT134 were active against T. vaginalis with an IC50 of 4.58 and 10.24 μM, respectively. These compounds were not toxic to epithelial cells in culture. Scanning electron microscopy observations revealed a rounding of the cells, a shortening of the flagella, and protrusions on the surface of drug-treated cells. Transmission electron microscopy of treated cells revealed alterations in the plasma membrane with formations of blebs, protrusions, depressions, and vacuoles with myelin figures and vacuolization in the cytoplasm after incubation. Furthermore, after treatments with the compounds LDT117 and LDT134, the parasites presented a positive reaction for TUNEL, indicating death by a mechanism like apoptosis. Given the results obtained, further in vivo studies using animal experimental models are necessary to validate that these compounds are effective for treating human trichomoniasis.

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来源期刊
Experimental parasitology
Experimental parasitology 医学-寄生虫学
CiteScore
3.10
自引率
4.80%
发文量
160
审稿时长
3 months
期刊介绍: Experimental Parasitology emphasizes modern approaches to parasitology, including molecular biology and immunology. The journal features original research papers on the physiological, metabolic, immunologic, biochemical, nutritional, and chemotherapeutic aspects of parasites and host-parasite relationships.
期刊最新文献
Effects of cardanol-based phospholipid analogs on Trichomonas vaginalis Fosfatriclaben: Effective dose determination and comparative efficacy assessment with closantel, triclabendazole+ivermectin, triclabendazole+albendazole in artificially infected cattle Editorial Board Imaging Giardia intestinalis cellular organisation using expansion microscopy reveals atypical centrin localisation Evaluation of muscular apoptotic changes and myogenin gene expression in experimental trichinosis after stem cells and atorvastatin added to ivermectin treatment
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