Praziquantel and liposomized glucan-treatment modulated liver fibrogenesis and mastocytosis in mice infected with Mesocestoides vogae (M. corti, Cestoda) tetrathyridia.
Beta-glucans are immunomodulators able to activate innate immunity and to potentiate acquired immune reactions. We investigated the impact of co-administration of liposomized beta-glucan on the larvicidal effect of the anthelmintic praziquantel (PZQ) in the livers and peritoneal cavities in mice infected with Mesocestoides vogae (M. corti). Also, within 2 weeks following therapy (up to day 29 p.i.) we examined collagen synthesis in the livers of mice by means of biochemical determination of hydroxyproline concentration, total mast cell counts and cell proliferative capacity using immunohistochemical and radiometrical methods. After co-administration of liposomized glucan (LG) and PZQ efficacy (%) was significantly higher than after treatment with either compound alone, particularly in the peritoneal cavity compared to the liver. In comparison with the control, more intense collagenesis was found in the B-liver parts (high intensity of infection) and lowering of collagen content in the A-parts (very weak infection). This effect was strongest after LG treatment and co-administration of PZQ abolished the pro-fibrotic effect of LG. In all groups, mast cell counts were higher in the B-liver parts than in the A-parts and the dynamics of mastocytosis was profoundly modulated following therapy. Whereas the effect of PZQ was only moderate, early and very strong onset was seen after LG treatment. Administration of PZQ suppressed LG induced-elevation of mast cells counts in both liver parts. Using DNA S-phase markers (BrdU and 3H-thymidine) the proliferative capacity was shown to be associated with several kinds of liver cells. Therapy significantly stimulated [3H]-thymidine incorporation (cell proliferation) only in the A-parts over that in control, the most after LG administration. In summary (i) the anthelmintic effect of PZQ could be enhanced after simultaneous administration of the immunomodulator beta-glucan entrapped in a liposomal carrier, (ii) intense mastocytosis seen after treatment with LG seems to have a direct role in the glucan's pro-fibrotic activity and can be abolished after co-administration of PZQ in a time-dependent manner, (iii) the pattern of cell proliferation indicates that in the case of PZQ treatment, the reparative processes of liver parenchyma are enhanced in an inverse correlation with the intensity of infection.
Parasitological Institute of the Slovak Academy of Sciences, Hlinkova 3, 04001 Kosice, Slovak Republic. hrcka@saske.sk
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Hrckova
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Velebný
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Daxnerová
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Solár
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000032:analysis; D002590:Cestode Infections / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004359:Drug Therapy, Combination; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D008081:Liposomes; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008415:Mastocytosis / Q000473:pathology / Q000517:prevention & control*; D008645:Mesocestoides / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D011223:Praziquantel / Q000008:administration & dosage / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014048:Tolonium Chloride / Q000378:metabolism; D014316:Tritium; D047071:beta-Glucans / Q000008:administration & dosage / Q000494:pharmacology*
D000871:Anthelmintics; D008081:Liposomes; D047071:beta-Glucans; D014316:Tritium; D014048:Tolonium Chloride; D011223:Praziquantel; D003094:Collagen; D001973:Bromodeoxyuridine; D006909:Hydroxyproline; D013936:Thymidine