Impact of treatment with praziquantel, silymarin and/or beta-glucan on pathophysiological markers of liver damage and fibrosis in mice infected with Mesocestoides vogae (Cestoda) tetrathyridia.
Mesocestoides vogae tetrathyridia infection in mice causes hepatocyte injury, hepatic granulomatous inflammmation, liver fibrosis and chronic peritonitis manifested with portal hypertension. To reduce the detrimental effect of parasites on the host liver, the effect of the anthelmintic drug praziquantel (PZQ) in combination with natural products silymarin (an antioxidant) and beta-glucan (an immunomodulator) was investigated. The therapeutic effect of drugs was assessed by means of aminotransferase (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) activities, content of albumin, total proteins and hyaluronic acid (HA) in sera of ICR mice infected with M. vogae larvae. Animals were treated with PZQ suspended in oil emulsion (Group 1), PZQ combined with silymarin incorporated into lipid microspheres (LMS) (Group 2), PZQ combined with beta-glucan incorporated into liposomes (LG) (Group 3), PZQ co-administered with LMS and LG (Group 4). Untreated animals (Group 5) served as the control. Treatment of animals started at the early chronic phase of infection (day 14 p.i.) and lasted 10 days; serum samples were collected on days 0, 7, 14, 25, 28, 31, 35 and 45 p.i. ALT and AST activities were significantly (P < 0.05) decreased in Groups 2, 3 and 4. HA content was significantly (P < 0.05 and 0.01) lower in Groups 2 and 4. Albumin levels were decreased in Groups 2 and 4, total protein concentration decreased in Groups 1 and 3 (P < 0.05 and 0.01). These results showed that combined treatment of PZQ with silymarin and/or beta-glucan was able to ameliorate or suppress fibrogenesis in the liver, protect liver cells from oxidative damage and, possibly, stimulate regeneration of the parenchyma.
Velebný
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S
Parasitological Institute, Slovak Academy of Sciences, Hlinkova 3, Kosice, Slovak Republic.
Hrckova
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Kogan
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G
D000410:Alanine Transaminase / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D001219:Aspartate Aminotransferases / Q000494:pharmacology; D002590:Cestode Infections; D004359:Drug Therapy, Combination; D006975:Hypertension, Portal / Q000188:drug therapy*; D007155:Immunologic Factors / Q000008:administration & dosage; D008099:Liver / Q000293:injuries* / Q000469:parasitology; D008109:Liver Diseases, Parasitic / Q000188:drug therapy*; D008297:Male; D008645:Mesocestoides / Q000187:drug effects / Q000302:isolation & purification*; D051379:Mice; D008813:Mice, Inbred ICR / Q000469:parasitology*; D010529:Peritoneal Cavity / Q000469:parasitology; D011223:Praziquantel / Q000008:administration & dosage; D012838:Silymarin / Q000008:administration & dosage; D047071:beta-Glucans / Q000008:administration & dosage
D000871:Anthelmintics; D000975:Antioxidants; D007155:Immunologic Factors; D012838:Silymarin; D047071:beta-Glucans; D011223:Praziquantel; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase