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- Title
Impaired liver regeneration following partial hepatectomy using the Pringle maneuver: Protective effect of mesna.
- Authors
Ypsilantis, Petros; Lambropoulou, Maria; Tentes, Ioannis; Anagnostopoulos, Konstantinos; Tsigalou, Christina; Papadopoulos, Nikolaos; Kortsaris, Alexandros; Simopoulos, Constantinos
- Abstract
Background and Aim: 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-κB (NF-κB) activity were assessed. Results: Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF-κB 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-κB 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-κB, while attenuating liver injury after PH under Pringle. Conclusion: The excessive activation of NF-κB 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-κB activation.
- Subjects
LIVER regeneration; HEPATECTOMY; ANTIOXIDANTS; SULFONATES; AMINOTRANSFERASES; ISCHEMIA
- Publication
Journal of Gastroenterology & Hepatology, 2009, Vol 24, Issue 4, p623
- ISSN
0815-9319
- Publication type
Article
- DOI
10.1111/j.1440-1746.2008.05641.x