维格列汀和二氨基二苯砜对小鼠曼氏血吸虫病的抗纤维化作用。

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Amira S Hendawy, Abdel-Nasser A Sabra, Mina Y George, Eman Rashad, Ebtehal El-Demerdash, Sanaa S Botros
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引用次数: 0

摘要

血吸虫病严重影响人类健康,曼氏梭菌引起的肝纤维化仍然是一个严重的问题,目前还没有可用的药物。本研究旨在评估维格列汀(Vildagliptin, Vilda)、二氨基二苯砜(Diaminodiphenyl Sulfone, DDS)及其联合用药(Vilda/DDS)对曼森链球菌诱导的肝纤维化的保护作用,并阐明其潜在的分子机制。mansoni感染小鼠连续2天给予吡喹酮(PZQ),或连续14天给予Vilda、DDS和Vilda/DDS。血吸虫病引起的肝纤维化进行了寄生虫学、生化和病理学评估。结果显示,Vida、DDS和Vida/DDS治疗可显著降低肉芽肿虫虫数、卵图分期、卵数,改善肉芽肿炎症反应和肝毒性指标。此外,它们还能增强肝脏Nrf2/HO-1通路,显著提高SOD水平,降低MDA水平。此外,它们显著下调肝脏TLR4/NF-κB和NLRP3炎症小体通路,导致TNF-α和caspase-1水平显著降低,这在IL-1β和caspase-3的激活中很重要。值得注意的是,肝脏TGF-β1、α-SMA和MMP-9的表达也显著下调。总之,与单独使用Vilda或DDS相比,Vilda/DDS对S. mansoni诱导的肝纤维化具有抗氧化、抗炎和抗纤维化活性。因此,Vilda/DDS是治疗曼氏梭菌感染、肝纤维化和相关疾病发病率的一种很有前景的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni.

Schistosomiasis drastically affects human health, where S. mansoni-induced hepatic fibrosis remains a serious problem with no available drug yet. The current study aimed to evaluate the hepatoprotective effects of Vildagliptin (Vilda), Diaminodiphenyl Sulfone (DDS), and their combination (Vilda/DDS) against S. mansoni-induced hepatic fibrosis and elucidate their underlying molecular mechanisms. S.mansoni-infected mice were administered praziquantel (PZQ) for two consecutive days, or Vilda, DDS, and Vilda/DDS for 14 consecutive days. Schistosomiasis-induced hepatic fibrosis was assessed parasitologically, biochemically, and pathologically. Results revealed that Vilda, DDS, and Vida/DDS treatments significantly reduced worm count, oogram stages, ova count, and ameliorated the granulomatous inflammatory reactions and hepatotoxicity indices. Moreover, they enhanced hepatic Nrf2/HO-1 pathway with significant increasing SOD and reducing MDA levels. Furthermore, they significantly downregulated the hepatic TLR4/NF-κB and NLRP3 inflammasome pathways leading to a significant reduction in TNF-α and caspase-1 levels which is important in the activation of IL-1β and caspase-3. Notably, significant downregulation in hepatic TGF-β1, α-SMA, and MMP-9 expressions were also recorded. In conclusion, Vilda/DDS showed antioxidant, anti-inflammatory and antifibrotic activities in comparison to either Vilda or DDS alone against S. mansoni-induced hepatic fibrosis. Therefore, Vilda/DDS is a promising approach for managing S. mansoni infection, liver fibrosis, and associated disease morbidity.

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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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