title: Specific type IV phosphodiesterase inhibitor ameliorates thioacetamide-induced liver injury in rats.
abstract: OBJECTIVE
  Rolipram is a specific type IV phosphodiesterase inhibitor that suppresses the activity of immune cells and the production of pro-inflammatory cytokines. In this study, we assessed the effect of rolipram on acute liver injury using thioacetamide (TAA)-induced liver injury in rats as a model.
  
  
  METHODS
  Rats were treated with rolipram (0.5-5 mg/kg, intraperitoneally) or vehicle and injected 30 min later with TAA (100 mg/kg, subcutaneously). Serum transaminase concentrations and tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta) and growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) levels were measured and livers were examined for microscopic changes. Dose-dependent protection against TAA liver injury was based on transaminase levels and inflammatory cytokine production, and was measured 9 h after TAA when the peak release of cytokines occurred.
  
  
  RESULTS
  Rolipram suppressed liver injury based on serum aspartate transaminase (AST), alanine transaminase (ALT) and histology and reduced TNF-alpha, IL-1beta and GRO/CINC-1 levels. Rolipram, at doses of 0.5-5 mg/kg, suppressed serum transaminase and TNF-alpha production in a dose-dependent manner, and these effects were significant at doses of 2.5 and 5 mg/kg.
  
  
  CONCLUSIONS
  In our rodent model of acute liver injury, rolipram clearly reduced liver damage and inhibited pro-inflammatory cytokine production. These results suggest that specific type IV phosphodiesterase inhibitors, such as rolipram, have potent hepatoprotective effects that are associated with suppressing inflammatory cytokine production.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, Akita City, Akita, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Mario
authors.initials: M
authors.lastname: Jin
authors.forename: Koga
authors.initials: K
authors.lastname: Komatsu
authors.forename: Noriaki
authors.initials: N
authors.lastname: Konishi
authors.forename: Isao
authors.initials: I
authors.lastname: Wada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sato
authors.forename: Youhei
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Reina
authors.initials: R
authors.lastname: Ohba
authors.forename: Jinko
authors.initials: J
authors.lastname: Oyake
authors.forename: Natsumi
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000627:therapeutic use*; D013853:Thioacetamide / Q000009:adverse effects*
chemical_list: D010726:Phosphodiesterase Inhibitors; D013853:Thioacetamide; D020889:Rolipram