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塞来昔布单独及与螺旋霉素联合应用对实验小鼠的抗弓形虫作用

Anti-toxoplasmic effects of celecoxib alone and combined with spiramycin in experimental mice.

作者信息

Shendi Sawsan S, Selim Sahar M, Sharaf Soraya A, Gouda Marwa A, Sallam Hebatallah M, Sweed Dina M, Shafey Dalia A

机构信息

Department of Clinical and Molecular Parasitology, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt.

Department of Clinical and Molecular Parasitology, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt.

出版信息

Acta Trop. 2024 Dec;260:107448. doi: 10.1016/j.actatropica.2024.107448. Epub 2024 Oct 28.

Abstract

Even though toxoplasmosis is a worldwide parasitic disease caused by Toxoplasma gondii (T. gondii), the available drugs used for the treatment of symptomatic toxoplasmosis have multiple drawbacks. So, there is a considerable need to discover new potential therapeutic agents. The current study aimed to assess the effect of celecoxib (CELE) alone or combined with spiramycin against chronic toxoplasmosis in experimentally infected mice. The study documented the reduction rate of T. gondii cysts in brain tissues and ultrastructural changes through transmission electron microscopy after treatment. We also investigated pathological changes in the brain, liver, lung, and spleen, as well as the expression of TGF-β, iNOS, and pSTAT-1 in brain tissues. Other markers for kidney function and serum levels of interleukins 10 and 12 were also assessed. The study reported a reduction rate of T. gondii brain cyst count of 32.9 % after CELE treatment, 71.7 % after spiramycin treatment, and 75.7 % after combined treatment. Furthermore, the CELE and spiramycin combination improved the ultrastructure and histopathology in brain tissues while decreasing TGF-β, iNOS, and pSTAT-1 expression. The combined therapy ameliorated the inflammation of the liver, lung, and spleen, upregulated the IL-12 level, reduced the IL-10 level, and was accompanied by a reduction in creatinine and urea in serum. In conclusion, CELE increased spiramycin therapeutic efficacy, and their combination showed a better response than spiramycin alone. Thus, the CELE combination with spiramycin represents a hopeful therapy against chronic toxoplasmosis.

摘要

尽管弓形虫病是一种由刚地弓形虫引起的全球性寄生虫病,但用于治疗有症状弓形虫病的现有药物存在多种缺陷。因此,迫切需要发现新的潜在治疗药物。本研究旨在评估塞来昔布(CELE)单独或与螺旋霉素联合使用对实验感染小鼠慢性弓形虫病的影响。该研究记录了治疗后通过透射电子显微镜观察到的脑组织中弓形虫囊肿的减少率和超微结构变化。我们还研究了脑、肝、肺和脾的病理变化,以及脑组织中转化生长因子-β(TGF-β)、诱导型一氧化氮合酶(iNOS)和磷酸化信号转导和转录激活因子1(pSTAT-1)的表达。还评估了肾功能的其他标志物以及白细胞介素10和12的血清水平。该研究报告称,CELE治疗后弓形虫脑囊肿计数减少率为32.9%,螺旋霉素治疗后为71.7%,联合治疗后为75.7%。此外,CELE与螺旋霉素联合使用改善了脑组织的超微结构和组织病理学,同时降低了TGF-β、iNOS和pSTAT-1的表达。联合治疗减轻了肝、肺和脾的炎症,上调了白细胞介素12水平,降低了白细胞介素10水平,并伴有血清肌酐和尿素的降低。总之,CELE提高了螺旋霉素的治疗效果,二者联合使用比单独使用螺旋霉素表现出更好的反应。因此,CELE与螺旋霉素联合使用是治疗慢性弓形虫病的一种有希望的疗法。

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