title: Hepatoprotective effects of early pentoxifylline administration on hepatic injury induced by concanavalin A in rat.
abstract: Tumor necrosis factor alpha (TNF-α) plays an important role in the pathogensis of hepatitis C virus (HCV) infection induced liver injury. This study aimed to evaluate the effects of TNF-α inhibition with pentoxifylline (PTX) on concanavalin A (Con A)-induced hepatic injury in rats. The rats were distributed among 3 groups: (i) control group (1 mL saline·week(-1) by intravenous injection (i.v.)); (ii) Con A treatment group (20 mg Con A·(kg body mass)(-1)·week(-1), i.v.), and (iii) rats treated with Con A and with PTX (200 mg PTX·(kg body mass)(-1)·day(-1), per oral) group. Blood samples and livers were collected at the end of weeks 1, 2, 4, and 8 of Con A treatment. Portal pressure (PP) was measured at the end of week 8. The administration of PTX was found to confer significant protection against the injurious effects of Con A on the liver, by reducing serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic TNF-α, and malondialdehyde. Histopathological examination revealed that treatment with PTX significantly suppressed early inflammation, reduced alpha smooth muscle actin, and the apoptosis of hepatocytes induced by Con A. Moreover, PTX significantly (P < 0.05) reduced PP, and quantitative analyses of the area of fibrosis induced by treatment with Con A showed a significant reduction at the end of week 8. We conclude that rats treated with PTX revealed a more or less normal hepatocyte architecture as well as marked improvement in fibrosis and PP.
authors.affiliation: a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Doaa Ibrahim
authors.initials: DI
authors.lastname: Mohamed
authors.forename: Ahmed Abdel Salam Mohamed
authors.initials: AA
authors.lastname: Elmelegy
authors.forename: Lubna Foaad A
authors.initials: LF
authors.lastname: El-Aziz
authors.forename: Hala Salah
authors.initials: HS
authors.lastname: Abdel Kawy
authors.forename: Abeer Ahmed
authors.initials: AA
authors.lastname: AbdEl-Samad
authors.forename: Omnyah Ali
authors.initials: OA
authors.lastname: El-Kharashi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003208:Concanavalin A / Q000633:toxicity*; D005355:Fibrosis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017082:Portal Pressure / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D010726:Phosphodiesterase Inhibitors; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010431:Pentoxifylline
keywords: concanavalin A; concanavaline A; facteur nécrosant des tumeurs alpha; malondialdehyde; malondialdéhyde; pentoxifylline; portal pressure; pression portale; tumor necrosis factor alpha