title: Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis.
abstract: BACKGROUND
  Praziquantel (PZQ) is an isoquinoline derivative (2-cyclohexylcarbonyl-1, 2, 3, 6, 7, 11b-hexahydro-4H-pyrazino{2,1-a}-isoquinoline-4-one), and is currently the drug of choice for all forms of schistosomiasis. Silymarin, a standardized milk thistle extract, of which silibinin is the main component, is known for its hepatoprotective, anti-inflammatory, antioxidant activities, and hepatocyte regeneration. This study investigates the anti-inflammatory/anti-fibrotic effects of silymarin and/or PZQ on schistosomal hepatic fibrosis.
  
  
  METHODS
  Schistosoma mansoni-infected mice were divided into two large groups (I & II), each with four subgroups and were run in parallel. (i) Infected untreated; (ii) treated with silymarin, starting from the 4th (3 weeks before PZQ therapy) or 12th (5 weeks after PZQ therapy) weeks post infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with silymarin, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice run in parallel with the infected groups. Mice of groups I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), transforming growth factor-β1 (TGF-β1) and number of mast cells were determined. In addition, parasitological, biochemical and histological parameters that reflect disease severity and morbidity were examined.
  
  
  RESULTS
  Silymarin caused a partial decrease in worm burden; hepatic tissue egg load, with an increase in percentage of dead eggs; modulation of granuloma size, with significant reduction of hepatic HYP content; tissue expression of MMP-2, TGF-β1; number of mast cells, with conservation of hepatic reduced glutathione (GSH). PZQ produced complete eradication of worms, eggs and alleviated liver inflammation and fibrosis. The best results were obtained, in most parameters studied, in groups of mice treated with silymarin in addition to PZQ.
  
  
  CONCLUSIONS
  Our results point to silymarin as a promising anti-inflammatory and anti-fibrotic agent; it could be introduced as a therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis, but further studies on mechanisms of silymarin and PZQ in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.
authors.affiliation: Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P,O Box 30, Giza 12411, Egypt. naglaaellakkany@yahoo.com
authors.forename: Naglaa M
authors.initials: NM
authors.lastname: El-Lakkany
authors.forename: Olfat A
authors.initials: OA
authors.lastname: Hammam
authors.forename: Walaa H
authors.initials: WH
authors.lastname: El-Maadawy
authors.forename: Afkar A
authors.initials: AA
authors.lastname: Badawy
authors.forename: Afaf A
authors.initials: AA
authors.lastname: Ain-Shoka
authors.forename: Fatma A
authors.initials: FA
authors.lastname: Ebeid
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination; D006909:Hydroxyproline / Q000097:blood; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000469:parasitology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D051379:Mice; D010270:Parasite Egg Count; D011223:Praziquantel / Q000008:administration & dosage*; D020011:Protective Agents / Q000008:administration & dosage*; D012550:Schistosoma mansoni / Q000187:drug effects; D012555:Schistosomiasis mansoni / Q000150:complications / Q000188:drug therapy*; D012556:Schistosomicides / Q000008:administration & dosage*; D012838:Silymarin / Q000008:administration & dosage*; D053773:Transforming Growth Factor beta1 / Q000032:analysis
chemical_list: D020011:Protective Agents; D012556:Schistosomicides; D012838:Silymarin; D053773:Transforming Growth Factor beta1; D011223:Praziquantel; D020778:Matrix Metalloproteinase 2; D006909:Hydroxyproline