title: Theophylline, an old drug with multi-faceted effects: Its potential benefits in immunological liver injury in rats.
abstract: OBJECTIVE
  A low dose of theophylline enhances histone deacetylase activity leading to inhibition of proinflammatory transcription, and inhibits lung fibroblast proliferation. The present work investigated the effect of lowdose theophylline on biochemical and histological pictures of liver tissues in rats with immunological hepatic injury induced by concanavalin A (Con A).
  
  
  METHODS
  Ratswere assigned to control vehicle,model (Con A) and theophylline groups. Half of the animals in each group were sacrificed at the end of the 4th week and the other half were sacrificed at the end of the 8th week.
  
  
  RESULTS
  There was a time-dependent increase in the liver injury parameters by the end of the 4th and 8th weeks in the Con A treated group. Theophylline (20 mg/kg/day), produced a significant decrease in serum liver enzymes (ALT, AST), serum interferon gamma (IFN-γ) levels and the hepatic transforming growth factor-β (TGF-β) level. A significant decrease in liver tissue hydroxyproline content together with reduction in portal hypertension at the end of the 8th week was detected compared to the Con A group. Theophylline treated rats exhibited a significant decrease in hepatic vacuolation, apoptosis, leucocyte infiltration, and accumulation of collagen fibers in comparison to the Con A group. In addition, significant decreases in the area percentage of fibrosis and the area percentage of caspase +ve cells were reported compared to the Con A group.
  
  
  CONCLUSIONS
  Theophylline effectively reduced the inflammation of liver tissues and alleviated the liver damage by decreasing IFN-γ and TGF-β in liver tissues of rats with immunological hepatic injury.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Egypt.
authors.forename: Reeham Mohamed
authors.initials: RM
authors.lastname: Hussein
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Egypt.
authors.forename: Osama Mahmod
authors.initials: OM
authors.lastname: Elsirafy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Egypt.
authors.forename: Yousria Saad
authors.initials: YS
authors.lastname: Wahba
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Egypt. Electronic address: halapharmacology@yahoo.com.
authors.forename: Hala Salah Abdel
authors.initials: HS
authors.lastname: Kawy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Egypt.
authors.forename: Amany Helmy
authors.initials: AH
authors.lastname: Hasanin
authors.affiliation: Department of Histology, Faculty of Medicine, Ain Shams University, Egypt.
authors.forename: Ghada Galal
authors.initials: GG
authors.lastname: Hamam
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D006909:Hydroxyproline / Q000378:metabolism; D016898:Interferon-alpha / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D017082:Portal Pressure; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D016212:Transforming Growth Factor beta; D013806:Theophylline; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3; D006909:Hydroxyproline
keywords: Concanavalin A; Hydroxyproline; Portal hypertension; Theophylline