title: Impaired liver regeneration following partial hepatectomy using the Pringle maneuver: Protective effect of mesna.
abstract: OBJECTIVE
  We investigated the role of the prophylactic administration of the antioxidant 2-mercaptoethane sulfonate (mesna) on the hepatocyte-regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver.
  
  
  METHODS
  Wistar rats were subjected to PH (70% hepatectomy), 30 min Pringle maneuver, PH plus Pringle with or without mesna pretreatment (400 mg/kg, per os, 3 h before Pringle), or sham operation. At 24 h, 48 h, 72 h, and 1 week after operation, relative liver weight, hepatocyte mitotic activity (mitotic index), the histopathological score and serum aspartate aminotransferase, and alanine aminotransferase concentrations were assessed. At 1 h after operation, oxidative stress markers (glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity) and nuclear factor-kappaB (NF-kappaB) activity were assessed.
  
  
  RESULTS
  Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF-kappaB in hepatocytes, while causing tissue injury in the remnant liver. When PH was performed under Pringle maneuver, hepatocyte mitotic activity was substantially suppressed, although Pringle alone initiated a delayed regenerating response. Furthermore, Pringle maneuver deteriorated oxidative stress markers, markedly increased NF-kappaB activity, and aggravated tissue injury, as compared to hepatectomy alone. Mesna pretreatment prevented the Pringle-induced antimitotic effect and the induction of oxidative stress, inhibited the activation of NF-kappaB, while attenuating liver injury after PH under Pringle.
  
  
  CONCLUSIONS
  The excessive activation of NF-kappaB is related to the suppression of hepatocyte-regenerating activity following PH with concurrent liver ischemia. Mesna pretreatment protects the liver against the Pringle-induced antimitotic effect after PH via the prevention of oxidative stress and the inhibition of NF-kappaB activation.
authors.affiliation: Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece. pipsil@med.duth.gr
authors.forename: Petros
authors.initials: P
authors.lastname: Ypsilantis
authors.forename: Maria
authors.initials: M
authors.lastname: Lambropoulou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Tentes
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Anagnostopoulos
authors.forename: Christina
authors.initials: C
authors.lastname: Tsigalou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Alexandros
authors.initials: A
authors.lastname: Kortsaris
authors.forename: Constantinos
authors.initials: C
authors.lastname: Simopoulos
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods*; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D015080:Mesna / Q000494:pharmacology*; D008940:Mitotic Index; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D015080:Mesna