Impaired liver regeneration following partial hepatectomy using the Pringle maneuver: Protective effect of mesna

• Published in: Journal of gastroenterology and hepatology 2009-04, Vol.24 (4), p.623-632
• Main Authors: Ypsilantis, Petros, Lambropoulou, Maria, Tentes, Ioannis, Anagnostopoulos, Konstantinos, Tsigalou, Christina, Papadopoulos, Nikolaos, Kortsaris, Alexandros, Simopoulos, Constantinos
• Format: Article
• Language: English
• Subjects: 2-mercaptoethane sulfonate; Alanine Transaminase - metabolism; Animals; Antioxidants - pharmacology; Aspartate Aminotransferases - metabolism; Biological and medical sciences; Gastroenterology. Liver. Pancreas. Abdomen; Glutathione - metabolism; Hepatectomy - methods; ischemia; liver; Liver - blood supply; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver - surgery; Liver Regeneration - drug effects; Liver, biliary tract, pancreas, portal circulation, spleen; Malondialdehyde - metabolism; Medical sciences; Mesna - pharmacology; Mitotic Index; Models, Animal; NF-kappa B - metabolism; Organ Size; Oxidative Stress - drug effects; Rats; Rats, Wistar; regeneration; reperfusion; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Superoxide Dismutase - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Time Factors
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2008.05641.x

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.