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      In vivo assessment of the antischistosomal activity of curcumin loaded nanoparticles versus praziquantel in the treatment of Schistosoma mansoni

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          Abstract

          Schistosomiasis is a serious parasitic infection affecting millions worldwide. This study aimed to explore the anti-schistosomal activity of curcumin and curcumin loaded gold-nanoparticles (Cur-GNPs) with or without praziquantel (PZQ). We used six groups of the C57BL/6 mice in which five groups were infected with Schistosoma Mansoni (S. mansoni) cercariae and exhibited, separately, to different treatment regimens of curcumin, curcumin loaded nanoparticle, and PZQ, in addition to one untreated group which acts as a control. Mice were sacrificed at the 8th week where both worms and eggs were counted in the hepatic and porto-mesenteric vessels in the liver and intestine, respectively, in addition to a histopathological examination of the liver granuloma. Curcumin caused a significant reduction in the worms and egg count (45.45%) at the 3rd week. A significant schistosomicidal effect of PZQ was found in all groups. Cur-GNPs combined with PZQ 97.4% reduction of worm burden in the 3rd week and the highest reduction in the intestinal and hepatic egg content, as well, besides 70.1% reduction of the granuloma size. The results suggested the curcumin in combination with PZQ as a strong schistosomicidal regimen against S. mansoni as it alters the hematological, biochemical, and immunological changes induced.

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          Most cited references50

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          Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes.

          The immunological response of macrophages to physically produced pure Au and Ag nanoparticles (NPs) (in three different sizes) is investigated in vitro. The treatment of either type of NP at > or =10 ppm dramatically decreases the population and increases the size of the macrophages. Both NPs enter the cells but only AuNPs (especially those with smaller diamter) up-regulate the expressions of proinflammatory genes interlukin-1 (IL-1), interlukin-6 (IL-6), and tumor necrosis factor (TNF-alpha). Transmission electron microscopy images show that AuNPs and AgNPs are both trapped in vesicles in the cytoplasma, but only AuNPs are organized into a circular pattern. It is speculated that part of the negatively charged AuNPs might adsorb serum protein and enter cells via the more complicated endocytotic pathway, which results in higher cytotoxicity and immunological response of AuNPs as compared to AgNPS.
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            Biological properties of curcumin-cellular and molecular mechanisms of action.

            Curcuminoids, a group of phenolic compounds isolated from the roots of Curcuma longa (Zingiberaceae), exhibit a variety of beneficial effects on health and on events that help in preventing certain diseases. A vast majority of these studies were carried out with curcumin (diferuloyl methane), which is a major curcuminoid. The most detailed studies using curcumin include anti-inflammatory, antioxidant, anticarcinogenic, antiviral, and antiinfectious activities. In addition, the wound healing and detoxifying properties of curcumin have also received considerable attention. As a result of extensive research on the therapeutic properties of curcumin, some understanding on the cellular, molecular, and biochemical mechanism of action of curcumin is emerging. These findings are summarized in this review.
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              Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment.

              The efficacy of praziquantel against a Puerto Rican strain of Schistosoma mansoni was assessed using both in vivo and in vitro approach. The drug effective dose (50%) in the infected mouse model was about 30 times higher when determined against 28-day-old infections than against 7-week-old parasites. Single-sex female infections were also largely refractory to treatment and single-sex male infections moderately refractory, in comparison with bisexual infections. The in vitro approach consisted of overnight exposure of parasite cultures to various drug concentrations, followed by several days of culture in drug-free medium. In vitro results confirmed in vivo data and allowed for the observation of schistosome morphological phenomena after praziquantel exposure. Early worm contraction was observed in all cases, even after exposure to sub-lethal concentrations of praziquantel or upon exposure of the largely refractory 28-day-old schistosomes. In these instances, however, worms resumed movements and normal shape upon drug removal and were able to survive. The inference of these observations on the clinical use of praziquantel and on its mechanism of action is discussed.

                Author and article information

                Contributors
                marwaahmed2008@outlook.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                25 September 2020
                25 September 2020
                2020
                : 10
                : 15742
                Affiliations
                [1 ]GRID grid.411170.2, ISNI 0000 0004 0412 4537, Department of Medical Parasitology, Faculty of Medicine, , Fayoum University, ; Fayoum, Egypt
                [2 ]GRID grid.420091.e, ISNI 0000 0001 0165 571X, Department of Immunology and Parasitology, , Theodor Bilharz Research Institute, ; Giza, Egypt
                [3 ]GRID grid.420091.e, ISNI 0000 0001 0165 571X, Department of Pathology, , Theodor Bilharz Research Institute, ; Giza, Egypt
                Article
                72901
                10.1038/s41598-020-72901-y
                7519097
                32978497
                95310477-d85e-4b7f-a044-be2cdab09097
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 March 2020
                : 31 August 2020
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                © The Author(s) 2020

                Uncategorized
                drug discovery,diagnostics,drug delivery
                Uncategorized
                drug discovery, diagnostics, drug delivery

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