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评价奈必洛尔在弓形虫病实验模型中的疗效:寄生虫负荷减少和神经元保护的见解。

Assessment of nebivolol efficacy in experimental models of toxoplasmosis: insights into parasite burden reduction and neuronal protection.

机构信息

Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, Brazil.

Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (PARASITTOS), Faculdade de Medicina de Jundiaí, Jundiaí, Brazil.

出版信息

Parasitol Res. 2024 Aug 20;123(8):303. doi: 10.1007/s00436-024-08318-7.

DOI:10.1007/s00436-024-08318-7
PMID:39160298
Abstract

This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2 mg/kg/day and 4 mg/kg/day for 8 days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41 days post-infection and were evaluated after 10 days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4 mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV's potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV's mechanisms of action and its clinical application in managing toxoplasmosis.

摘要

本研究旨在探讨奈必洛尔(NBV)在弓形虫病实验模型中的疗效,重点关注寄生虫负担的减轻和神经元的保护。在急性弓形虫病实验模型中,感染 RH 株速殖子的瑞士小鼠接受了 2mg/kg/天和 4mg/kg/天的口服 NBV 盐酸盐治疗,共 8 天。与对照组相比,NBV 治疗显著降低了寄生虫负担。在慢性弓形虫病实验模型中,感染 ME49 株的 C57/BL6 小鼠在感染后第 41 天接受 NBV 盐酸盐治疗,并在治疗 10 天后进行评估。NBV 盐酸盐与对照组相比,有效降低了囊泡数量和面积,以及缓殖子负担。组织学分析表明,NBV 盐酸盐保留了神经元计数,4mg/kg/天剂量的神经元计数与未感染的小鼠相似。统计分析证实与对照组相比有显著差异。此外,免疫组织化学分析显示,NBV 盐酸盐治疗的小鼠大脑中的 iNOS 标记明显减少,表明与对照组相比,NO 生成减少。这些发现表明 NBV 作为弓形虫病治疗的有前途的候选药物的潜力,突出了其降低寄生虫负担和保护神经元完整性的能力。需要进一步研究来阐明 NBV 的作用机制及其在弓形虫病治疗中的临床应用。

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