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脱氢甲状腺原氨酸对皮肤利什曼病的作用:小鼠模型中的治疗结果

Dehydrothyrsiferol Against Cutaneous Leishmaniasis: Treatment Outcome in a Murine Model.

作者信息

López-Arencibia Atteneri, Bethencourt-Estrella Carlos J, San Nicolás-Hernández Desirée, Rodríguez-Expósito Rubén L, Domínguez-de-Barros Angélica, Salazar-Villatoro Lizbeth, Omaña-Molina Maritza, Cen-Pacheco Francisco, Díaz-Marrero Ana R, Fernández José J, Córdoba-Lanús Elizabeth, Lorenzo-Morales Jacob, Piñero José E

机构信息

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avenida Astrofísico Francisco Sánchez s/n, 38206 La Laguna, Spain.

Consorcio Centro de Investigación Biomédica en Red M.P. de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28006 Madrid, Spain.

出版信息

Mar Drugs. 2024 Dec 28;23(1):13. doi: 10.3390/md23010013.

Abstract

One of the most important steps in preclinical drug discovery is to demonstrate the in vivo efficacy of potential leishmanicidal compounds and good characteristics at the level of parasite killing prior to initiating human clinical trials. This paper describes the use of dehydrothyrsiferol (DT), isolated from the red alga , in a pharmaceutical form supported on Sepigel, and the in vivo efficacy against a mouse model of cutaneous leishmaniasis. Studying the ultrastructural effect of DT was also carried out to verify the suspected damage at the cellular level and determine the severity of damages produced in the homeostasis of promastigotes. BALB/c mice infected with were divided into four groups: untreated mice, mice treated with miltefosine orally and mice treated topically with 1% and 0.5% DT-Sepigel; treatment was carried out for two weeks. Treatment with DT significantly reduced the parasite load in skin, liver and spleen compared with the untreated group. In addition, DT-Sepigel at the lowest concentration (0.5%) showed the best results, reducing lesion size by 87% at 3 weeks post-treatment. DT-Sepigel has demonstrated to be a potent topical treatment that, in combined drug trials, may aim at combating cutaneous leishmaniasis.

摘要

临床前药物发现中最重要的步骤之一是在启动人体临床试验之前,证明潜在的杀利什曼原虫化合物的体内疗效以及在寄生虫杀灭水平上的良好特性。本文描述了从红藻中分离出的脱氢扁枝石松醇(DT)在Sepigel载体上制成药物剂型的应用,以及对皮肤利什曼病小鼠模型的体内疗效。还研究了DT的超微结构效应,以验证在细胞水平上的可疑损伤,并确定前鞭毛体稳态中产生的损伤严重程度。感染了的BALB/c小鼠分为四组:未治疗的小鼠、口服米替福新治疗的小鼠以及分别用1%和0.5%DT-Sepigel局部治疗的小鼠;治疗持续两周。与未治疗组相比,DT治疗显著降低了皮肤、肝脏和脾脏中的寄生虫负荷。此外,最低浓度(0.5%)的DT-Sepigel显示出最佳效果,在治疗后3周时将病变大小减少了87%。DT-Sepigel已被证明是一种有效的局部治疗方法,在联合药物试验中,可能旨在对抗皮肤利什曼病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5599/11766930/66b390606fcd/marinedrugs-23-00013-g001.jpg

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