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在实验感染小鼠的慢性弓形虫病期间,他莫昔芬增加了寄生虫负荷,并引发了一系列组织病理学和免疫组织化学变化。

Tamoxifen Increased Parasite Burden and Induced a Series of Histopathological and Immunohistochemical Changes During Chronic Toxoplasmosis in Experimentally Infected Mice.

作者信息

Barakat Ashraf Mohamed, El Fadaly Hassan Ali Mohamed, Selem Rabab Fawzy, Madboli Abd El-Nasser A, Abd El-Razik Khaled A, Hassan Ehssan Ahmed, Alghamdi Ali H, Elmahallawy Ehab Kotb

机构信息

Department of Zoonotic Diseases, Veterinary Research Institute, National Research Centre, Giza, Egypt.

Department of Parasitology, Faculty of Medicine, Benha University, Benha, Egypt.

出版信息

Front Microbiol. 2022 May 30;13:902855. doi: 10.3389/fmicb.2022.902855. eCollection 2022.

Abstract

The global distribution of breast cancer and the opportunistic nature of the parasite have resulted in many patients with breast cancer becoming infected with toxoplasmosis. However, very limited information is available about the potential effects of tamoxifen on chronic toxoplasmosis and its contribution to the reactivation of the latent infection. The present study investigated the potential effects of tamoxifen on chronic toxoplasmosis in animal models (Swiss albino mice). Following induction of chronic toxoplasmosis and treatment with the drug for 14 and 28 days, the anti-parasitic effects of tamoxifen were evaluated by parasitological assessment and counting of cysts. In addition, the effects of the drug on the parasite load were evaluated and quantitated using TaqMan real-time quantitative PCR followed by investigation of the major histopathological changes and immunohistochemical findings. Interestingly, tamoxifen increased the parasite burden on animals treated with the drug during 14 and 28 days as compared with the control group. The quantification of the DNA concentrations of gene after the treatment with the drug revealed a higher parasite load in both treated groups vs. control groups. Furthermore, treatment with tamoxifen induced a series of histopathological and immunohistochemical changes in the kidney, liver, brain, and uterus, revealing the exacerbating effect of tamoxifen against chronic toxoplasmosis. These changes were represented by the presence of multiple cysts in the lumen of proximal convoluted tubules associated with complete necrosis in their lining epithelium of the kidney section. Meanwhile, liver tissue revealed multiple tissue cysts in hepatic parenchyma which altered the structure of hepatocytes. Moreover, clusters of intracellular tachyzoites were observed in the lining epithelium of endometrium associated with severe endometrial necrosis and appeared as diffuse nuclear pyknosis combined with sever mononuclear cellular infiltration. Brain tissues experienced the presence of hemorrhages in pia mater and multiple tissue cysts in brain tissue. The severity of the lesions was maximized by increasing the duration of treatment. Collectively, the study concluded novel findings in relation to the potential role of tamoxifen during chronic toxoplasmosis. These findings are very important for combating the disease, particularly in immunocompromised patients which could be life-threatening.

摘要

乳腺癌的全球分布以及该寄生虫的机会性本质,导致许多乳腺癌患者感染弓形虫病。然而,关于他莫昔芬对慢性弓形虫病的潜在影响及其对潜伏感染再激活的作用,现有信息非常有限。本研究在动物模型(瑞士白化小鼠)中调查了他莫昔芬对慢性弓形虫病的潜在影响。在诱导慢性弓形虫病并用药治疗14天和28天后,通过寄生虫学评估和囊肿计数来评估他莫昔芬的抗寄生虫作用。此外,使用TaqMan实时定量PCR评估并定量药物对寄生虫负荷的影响,随后研究主要的组织病理学变化和免疫组化结果。有趣的是,与对照组相比,他莫昔芬在14天和28天治疗期间增加了用药动物的寄生虫负担。用药治疗后基因DNA浓度的定量显示,两个治疗组的寄生虫负荷均高于对照组。此外,他莫昔芬治疗在肾脏、肝脏、大脑和子宫中引起了一系列组织病理学和免疫组化变化,揭示了他莫昔芬对慢性弓形虫病的加剧作用。这些变化表现为近端曲管腔内存在多个囊肿,其肾段衬里上皮出现完全坏死。同时,肝组织显示肝实质内有多个组织囊肿,改变了肝细胞结构。此外,在子宫内膜衬里上皮中观察到细胞内速殖子簇,伴有严重的子宫内膜坏死,表现为弥漫性核固缩并伴有严重的单核细胞浸润。脑组织在软脑膜有出血,脑组织内有多个组织囊肿。随着治疗时间延长,病变严重程度加剧。总体而言,该研究得出了关于他莫昔芬在慢性弓形虫病中潜在作用的新发现。这些发现对于对抗该疾病非常重要,特别是在可能危及生命的免疫功能低下患者中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/9189418/368f8c35c2c4/fmicb-13-902855-g001.jpg

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