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Co-administration of silymarin elevates the therapeutic effect of praziquantel through modulation of specific antibody profiles, Th1/Th2/Tregs cytokines and down-regulation of fibrogenesis in mice with Mesocestoides vogae (Cestoda) infection
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SYSNO ASEP 0524734 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Co-administration of silymarin elevates the therapeutic effect of praziquantel through modulation of specific antibody profiles, Th1/Th2/Tregs cytokines and down-regulation of fibrogenesis in mice with Mesocestoides vogae (Cestoda) infection Author(s) Hrčková, G. (SK)
Kubašková Mačák, T. (SK)
Reiterová, K. (SK)
Biedermann, David (MBU-M) RID, ORCIDArticle number 107888 Source Title Experimental Parasitology. - : Elsevier - ISSN 0014-4894
Roč. 213, JUN (2020)Number of pages 11 s. Language eng - English Country US - United States Keywords Mesocestoides vogae ; Praziquantel ; Silymarin Subject RIV CE - Biochemistry OECD category Medicinal chemistry R&D Projects LTC18071 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support MBU-M - RVO:61388971 UT WOS 000534594500002 EID SCOPUS 85082858993 DOI 10.1016/j.exppara.2020.107888 Annotation Silymarin (SIL) represents a natural mixture of polyphenols showing an array of health benefits. The present study, carried out on a model cestode infection induced by Mesocestoides vogae tetrathyridia in the ICR strain of mice, was aimed at investigating the impact of SIL as adjunct therapy on the activity of praziquantel (PZQ) in relation to parasite burden, immunity and liver fibrosis within 20 days post-therapy. In comparison with PZQ alone, co-administration of SIL and PZQ stimulated production of total IgG antibodies to somatic and excretory-secretory antigens of metacestodes and modified the expression patterns of immunogenic molecules in both antigenic preparations. The combined therapy resulted in the elevation of IFN-gamma and a decline of TNF-alpha and TGF-beta 1 in serum as compared to untreated group, however, SIL attenuated significantly the effect of PZQ on IL-4 and stimulated PZQ-suppressed phagocytosis of peritoneal macrophages. In the liver, SIL boosted the effect of PZQ on gene expression of the same cytokines in a similar way as was found in serum, except for down-regulation of PZQ-stimulated TNF-alpha. Compared to PZQ therapy, the infiltration of mast cells into liver after SIL co-administration was nearly abolished and correlated with suppressed activities of genes for collagen I, collagen III and alpha-SMA. In conclusion, co-administration of SIL modified the effects of PZQ therapy on antigenic stimulation of the immune system and modulated Th1/Th2/Tregs cytokines. In liver this was accompanied by reduced fibrosis, which correlated with significantly higher reduction of total numbers of tetrathyridia after combined therapy as compared with PZQ treatment. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2021 Electronic address https://www.sciencedirect.com/science/article/pii/S0014489419302838
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