title: The use of pentoxifylline as adjuvant therapy with praziquantel downregulates profibrogenic cytokines, collagen deposition and oxidative stress in experimental schistosomiasis mansoni.
abstract: This study investigates the possible use of pentoxifylline (PTX), with antifibrotic and anti-inflammatory properties, as adjuvant in treatment of schistosomal liver fibrosis through determination of some profibrogenic cytokines, oxidative stress and collagen deposition. Animals were classified into seven groups: normal control (i), Schistosoma mansoni-infected untreated (ii), infected treated with praziquantel (PZQ) curative, 1000mg/kg (iii) or sub curative, 200mg/kg dose (iv), infected treated with PTX alone (10mg/kg/day; 5days/wk) for 8weeks starting from the 2nd to the 10th week post infection (v), or in addition to curative (vi) or sub curative dose of PZQ (vii). Serum transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), matrix metalloproteinases-2 (MMP-2) and hepatic hydroxyproline (Hyp) content, glutathione related antioxidant enzymes and malondialdehyde (MDA) were determined. Results showed that S. mansoni infection produced remarkable elevations in the serum levels of TGF-β1, TNF-α, MMP-2 and the hepatic contents of Hyp, glutathione reductase (GR), MDA with significant reduction in reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) when compared with their corresponding normal controls. Treatment of infected mice with PTX in addition to PZQ curative rather than its sub curative dose produced the best results evidenced by complete normalization in the previously mentioned serum and hepatic parameters.
  
  
  CONCLUSIONS
  PTX could attenuate liver fibrosis in early stages of S. mansoni infection through downregulation of profibrogenic cytokines, oxidative stress and collagen deposition.
authors.affiliation: Pharmacology Department, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt. naglaaellakkany@yahoo.com
authors.forename: Naglaa
authors.initials: N
authors.lastname: El-Lakkany
authors.forename: Sayed Seif
authors.initials: SS
authors.lastname: el-Din
authors.forename: Fatma
authors.initials: F
authors.lastname: Ebeid
mesh_terms: D000818:Animals; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D011223:Praziquantel / Q000627:therapeutic use*; D011897:Random Allocation; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000378:metabolism; D012556:Schistosomicides / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D012556:Schistosomicides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D011223:Praziquantel; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D006909:Hydroxyproline; D010431:Pentoxifylline