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

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Abstract

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, inducing 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 hepatocellular injury evidenced 1 week after hepatectomy.

Conclusions:

The presence of sinusoidal obstruction syndrome impairs hepatic regeneration in this rat model of sinusoidal obstruction syndrome.

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