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

IF 1.8 3区 医学 Q2 PARASITOLOGY Parasitology Research Pub Date : 2024-08-20 DOI:10.1007/s00436-024-08318-7
Amanda Bruno da Silva Bellini Ramos, Tayline Torres, Luis Felipe Cunha Dos Reis, Gabriel Carvalho Lambert, Fábio Antônio Colombo, Marcos José Marques, Juliana Quero Reimão
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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.

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评估奈必洛尔在弓形虫病实验模型中的疗效:对减轻寄生虫负担和保护神经元的见解。
本研究调查了奈必洛尔(NBV)在弓形虫病实验模型中的疗效,重点是减少寄生虫负担和保护神经元。在实验性弓形虫病急性模型中,感染了 RH 株速殖寄生虫的瑞士小鼠连续 8 天口服氯水 NBV,剂量分别为 2 毫克/千克/天和 4 毫克/千克/天。与车辆组和标准药物组(PYR)相比,NBV 治疗可明显减轻寄生虫负担。在实验性弓形虫病慢性模型中,感染 ME49 株的 C57/BL6 小鼠在感染后 41 天接受 NBV 氯水合物治疗,并在治疗 10 天后进行评估。与对照组相比,氯水合 NBV 能有效减少囊肿数量和面积,以及缓虫负担。组织学分析表明,氯水合 NBV 能保留神经元数量,4 毫克/千克/天的剂量产生的神经元数量与未感染小鼠相似。统计分析证实,与对照组相比,NBV 氯水合物对神经元数量有显著差异。此外,免疫组化分析表明,与对照组相比,接受氯水合 NBV 治疗的小鼠大脑中 iNOS 标记显著减少,表明一氧化氮的产生减少。这些研究结果表明,NBV 有潜力成为弓形虫病治疗的候选药物,它能够减轻寄生虫负担并保护神经元的完整性。我们有必要进一步研究 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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来源期刊
Parasitology Research
Parasitology Research 医学-寄生虫学
CiteScore
4.10
自引率
5.00%
发文量
346
审稿时长
6 months
期刊介绍: The journal Parasitology Research covers the latest developments in parasitology across a variety of disciplines, including biology, medicine and veterinary medicine. Among many topics discussed are chemotherapy and control of parasitic disease, and the relationship of host and parasite. Other coverage includes: Protozoology, Helminthology, Entomology; Morphology (incl. Pathomorphology, Ultrastructure); Biochemistry, Physiology including Pathophysiology; Parasite-Host-Relationships including Immunology and Host Specificity; life history, ecology and epidemiology; and Diagnosis, Chemotherapy and Control of Parasitic Diseases.
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