Hepatic regeneration is decreased in a rat model of sinusoidal obstruction syndrome.
OBJECTIVE
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.
Laboratoire de Physiopathologie Hépatique et Imagerie Moléculaire, Hôpitaux Universitaires de Genève, Geneva 1205, Switzerland.
Eduardo
E
Schiffer
Jean-Louis
JL
Frossard
Laura
L
Rubbia-Brandt
Gilles
G
Mentha
Catherine M
CM
Pastor
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004195:Disease Models, Animal; D006498:Hepatectomy; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000503:physiopathology* / Q000601:surgery; D008115:Liver Regeneration; D016686:Monocrotaline; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016686:Monocrotaline