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评估2-硝基咪唑的治疗效果:一项使用BALB/c小鼠的体外和体内研究

Evaluating The Therapeutic Effect of 2-Nitroimidazole on : An In vitro and In vivo Study Using BALB/c Mice.

作者信息

Ghiasipour Elaheh, Sadraei Javid, Ghaffarifar Fatemeh

机构信息

Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Iran J Pharm Res. 2025 Feb 24;24(1):e157086. doi: 10.5812/ijpr-157086. eCollection 2025 Jan-Dec.

Abstract

BACKGROUND

Toxoplasmosis, caused by the protozoan parasite , remains a significant health concern due to its widespread prevalence and severe impact on immunocompromised individuals. Current treatments are limited, necessitating the exploration of new therapeutic agents.

OBJECTIVES

This study aimed to evaluate the efficacy and safety of 2-nitroimidazole as a potential treatment for toxoplasmosis in BALB/c mice, comparing its effects with the standard treatment, sulfadiazine.

METHODS

In vitro assays were conducted to determine the half-maximal inhibitory concentration (IC50) of 2-nitroimidazole and sulfadiazine against tachyzoites. The MTT assay was used to assess the cytotoxicity of 2-nitroimidazole on macrophages. In vivo experiments involved treating BALB/c mice infected with with either 2-nitroimidazole or sulfadiazine, monitoring survival rates and therapeutic outcomes.

RESULTS

In vitro results revealed IC50 values of 5.43 μM for 2-nitroimidazole and 2.99 μM for sulfadiazine, indicating potent anti-tachyzoite activity. The MTT assay showed that 2-nitroimidazole had low cytotoxicity, with significant cell viability even at higher concentrations. Based on the MTT assay findings, 40 μM of 2-nitroimidazole showed the highest level of toxicity towards macrophages. Furthermore, flow cytometry analysis revealed that this compound induced apoptosis in approximately 58.9% of tachyzoites. In vivo, all mice in the control group died by the eighth day. Treatment with sulfadiazine resulted in two mice surviving until the 14th day, while 2-nitroimidazole treatment saw one mouse surviving to the same day. These findings suggest that 2-nitroimidazole has comparable efficacy to sulfadiazine with potentially fewer side effects.

CONCLUSIONS

The study demonstrates that 2-nitroimidazole is a promising candidate for the treatment of toxoplasmosis, exhibiting strong anti-parasitic activity and low cytotoxicity. Further research is warranted to optimize dosing regimens and explore combination therapies to enhance its therapeutic potential.

摘要

背景

由原生动物寄生虫引起的弓形虫病,因其广泛流行以及对免疫功能低下个体的严重影响,仍然是一个重大的健康问题。目前的治疗方法有限,因此需要探索新的治疗药物。

目的

本研究旨在评估2-硝基咪唑作为BALB/c小鼠弓形虫病潜在治疗药物的疗效和安全性,并将其效果与标准治疗药物磺胺嘧啶进行比较。

方法

进行体外试验以确定2-硝基咪唑和磺胺嘧啶对速殖子的半数抑制浓度(IC50)。采用MTT法评估2-硝基咪唑对巨噬细胞的细胞毒性。体内实验包括用2-硝基咪唑或磺胺嘧啶治疗感染的BALB/c小鼠,监测存活率和治疗效果。

结果

体外结果显示,2-硝基咪唑的IC50值为5.43μM,磺胺嘧啶为2.99μM,表明两者均具有强大的抗速殖子活性。MTT试验表明,2-硝基咪唑具有低细胞毒性,即使在较高浓度下细胞活力也显著。基于MTT试验结果,40μM的2-硝基咪唑对巨噬细胞的毒性最高。此外,流式细胞术分析显示,该化合物诱导约58.9%的速殖子凋亡。在体内,对照组的所有小鼠在第8天死亡。用磺胺嘧啶治疗有两只小鼠存活至第14天,而用2-硝基咪唑治疗有一只小鼠存活至同一天。这些发现表明,2-硝基咪唑与磺胺嘧啶疗效相当,且副作用可能更少。

结论

该研究表明,2-硝基咪唑是治疗弓形虫病的一个有前景的候选药物,具有强大的抗寄生虫活性和低细胞毒性。有必要进一步研究以优化给药方案并探索联合疗法,以增强其治疗潜力。

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