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与乙酰水杨酸相关及其与感染小鼠肝纤维化的关系

Associated with Acetylsalicylic Acid and Their Relation to the Hepatic Fibrosis in Infected Mice.

作者信息

Feitosa Karina A, Zaia Maurício G, Rodrigues Vanderlei, Castro Cynthia A, Correia Ricardo de O, Pinto Fábio G, Rossi Karina N Z P, Avó Lucimar R S, Afonso Ana, Anibal Fernanda F

机构信息

Laboratory of Inflammation and Infectious Diseases, Department of Morphology and Pathology, Universidade Federal de São Carlos, São Carlos, Brazil.

Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.

出版信息

Front Pharmacol. 2018 Jan 18;8:1000. doi: 10.3389/fphar.2017.01000. eCollection 2017.

Abstract

Schistosomiasis is an important parasitic disease caused by , an intravascular trematode. Schistosomiasis treatment is limited to just one drug, Praziquantel (PZQ). Thus, studies on new antischistosomal compounds are of fundamental importance to disease control. Here we report on the effects of L. compounds - menthol and menthone - in association with acetylsalicylic acid (ASA) in the regulation of hepatic fibrosis caused by schistosomiasis granulomas. Six different groups of Swiss rats were infected with 80 cercariae. Two groups received only menthol and menthol treatment at different concentrations (30 and 50 mg/kg); two groups received treatment with the same concentration of menthol and menthol, but associated the ASA. All groups received treatment for 14 consecutive days from the 35 days after the parasitic infection. In addition, three other groups were used: uninfected and untreated group, infected and untreated group and infected group treated with the commercial drug (single dose). Parasitological, cytological and histological analyses were performed. Results showed a significant reduction on the number of eosinophils found in the peritoneal cavity lavage (LPC) in all treated groups and on the number of eosinophils found in the blood of PZQ treated group, in the blood of the group treated with 30 mg/kg of Mentaliv and in the blood of group treated with 50 mg/kg Mentaliv + ASA when compared to the infected group. All treated groups presented a reduction in the parasite load, represented by the number of eggs, in the experimental group treated with 30 mg/kg of menthol and menthone a 62.80% reduction was observed and in the experimental group treated with 50 mg/kg of menthol and menthone + ASA a reduction of 64.21% was observed. In the liver histological analysis we observed that all Mentaliv treated groups expressed a unique cytological profile, with diffused cells through the granuloma. In the experimental group treated with 50 mg/kg of Mentaliv + ASA it was possible to observe the formation of type III collagen fibers, a typical wound healing characteristic. Our data strongly suggest that both the hepatic fibrosis and the inflammatory process were regulated through the schistosomiasis granulomatous process after treatment with menthol and menthone associated with ASA.

摘要

血吸虫病是一种由血管内吸虫引起的重要寄生虫病。血吸虫病的治疗仅限于一种药物,吡喹酮(PZQ)。因此,对新型抗血吸虫化合物的研究对于疾病控制至关重要。在此,我们报告L.化合物——薄荷醇和薄荷酮——与乙酰水杨酸(ASA)联合使用对血吸虫病肉芽肿所致肝纤维化的调节作用。将六组不同的瑞士大鼠感染80只尾蚴。两组分别接受不同浓度(30和50mg/kg)的薄荷醇和薄荷酮治疗;两组接受相同浓度的薄荷醇和薄荷酮治疗,但联合使用ASA。所有组从寄生虫感染后35天起连续治疗14天。此外,还使用了另外三组:未感染且未治疗组、感染且未治疗组以及用商业药物治疗的感染组(单剂量)。进行了寄生虫学、细胞学和组织学分析。结果显示,与感染组相比,所有治疗组腹腔灌洗(LPC)中嗜酸性粒细胞数量以及PZQ治疗组血液中、30mg/kg Mentaliv治疗组血液中以及50mg/kg Mentaliv + ASA治疗组血液中嗜酸性粒细胞数量均显著减少。所有治疗组的寄生虫负荷均有所降低,以虫卵数量表示,在接受30mg/kg薄荷醇和薄荷酮治疗的实验组中观察到减少了62.80%,在接受50mg/kg薄荷醇和薄荷酮 + ASA治疗的实验组中观察到减少了64.21%。在肝脏组织学分析中,我们观察到所有接受Mentaliv治疗的组均表现出独特的细胞学特征,细胞通过肉芽肿扩散。在接受50mg/kg Mentaliv + ASA治疗的实验组中,可以观察到III型胶原纤维的形成,这是典型的伤口愈合特征。我们的数据强烈表明,在与ASA联合使用薄荷醇和薄荷酮治疗后,血吸虫病肉芽肿过程对肝纤维化和炎症过程均有调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4441/5778335/82947b92b065/fphar-08-01000-g001.jpg

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