title: Effects of pirfenidone on endotoxin-induced liver injury after partial hepatectomy in rats.
abstract: BACKGROUND
  In living donor liver transplantation, restrictions on graft size are a serious obstacle to expand indications for adult recipients. The sequence of gram-negative infection, septicemia, and multiple-organ failure is a common cause of early mortality after liver transplantation. An effective therapy has not been established for endotoxemia following extended hepatectomy in donors or small-for-size grafts in recipients. Pirfenidone (PFD), a new experimental antifibrotic agent, was used to ameliorate on endotoxin-induced liver injury following partial hepatectomy.
  
  
  METHODS
  Male Sprague-Dawley rats were intravenously administered lipopolysaccharide (LPS) 48 hours after 70% hepatectomy. Prior to LPS administration, PFD (300 mg/kg) or its vehicle (0.5% carboxymethylcellulose) was given orally twice.
  
  
  RESULTS
  The survival rate of the PFD-treated group was markedly improved compared with that of the controls. PFD prevented the increases in the activities of serum enzymes (aspartate transaminase [AST], alanine transaminase [ALT], and lactate dehydrogenase [LDH]) and total bilirubin. The serum and liver tissue levels of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, interferon-gamma, and interleukin-6, were significantly lower among the PFD than the control group. Furthermore, the degree of necrosis in the remnant liver was significantly decreased in the PFD-treated rats compared with controls.
  
  
  CONCLUSIONS
  These results indicate that PFD alleviates endotoxin-induced liver injury after partial hepatectomy through the inhibition of production of inflammatory cytokines in the residual liver. PFD may be useful to prevent endotoxin-induced liver injury after hepatectomy.
authors.affiliation: Department of Surgery, Kansai Medical University, Osaka, Japan. kaibori@takii.kmu.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Kaibori
authors.forename: H
authors.initials: H
authors.lastname: Yanagida
authors.forename: N
authors.initials: N
authors.lastname: Yokoigawa
authors.forename: T
authors.initials: T
authors.lastname: Hijikawa
authors.forename: A-H
authors.initials: AH
authors.lastname: Kwon
authors.forename: T
authors.initials: T
authors.lastname: Okumura
authors.forename: Y
authors.initials: Y
authors.lastname: Kamiyama
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004731:Endotoxins / Q000633:toxicity*; D006498:Hepatectomy; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004731:Endotoxins; D008070:Lipopolysaccharides; D011728:Pyridones; C093844:pirfenidone