Hepatic Regeneration Is Decreased in a Rat Model of Sinusoidal Obstruction Syndrome

Background and Objectives: Oxaliplatin is a chemotherapeutic drug for colorectal adenocarcinoma able to extend the indications for resection of colorectal liver metastases. However. the drug may severely injure hepatic sinusoids. including a sinusoidal Obstruction syndrome in non-tumoral parenchyma with a risk of decreased regeneration in the remnant liver following partial hepatectomy. Methods: We then investigated the evolution of hepatic functions and liver regeneration following partial hepatectomy in rats, with sinusoidal Obstruction syndrome. The sinusoidal Obstruction syndrome was induced with a single intragastric administration of monocrotaline (MCT). Results: MCT administration induced Obstruction of the hepatic microcirculation and increased portal pressure, hepatic VEGF expression. and Ki67 positive hepatocytes. A mild cholestasis was present without modification of hepatic tests. Following a 70% hepatectomy. liver regeneration was significantly impaired by MCT administration and this impaired regeneration was associated with hapatocellular injury evidenced I week after hepatectomy. Conclusions: The presence of sinusoidal Obstruction syndrome impairs hepatic regeneration in this rat model of sinusoidal Obstruction syndrome. J. Surg. Oncol. 2009:99:439-446. (C) 2009 Wiley-Liss, Inc.